CN109096318B - Method for preparing organoboron compounds and β-hydroxy compounds catalyzed by supported copper ion Y-type molecular sieves - Google Patents

Abstract

The invention relates to a method for preparing organic boron compounds and β-hydroxy compounds by catalyzing a Y-type molecular sieve supported with copper ions. Wherein the preparation of organoboron compounds mainly includes the following steps: A. adding copper ion-loaded Y-type molecular sieves, tetrahydrofuran and water in the reaction vessel, and fully stirring at room temperature to obtain a mixed solution; B. adding α,β-unsaturated carbonyl to the mixed solution Compound and biboronic acid pinacol ester reagent; C. Fully react with stirring at room temperature; D. After the reaction, separate and purify to obtain. The method for preparing the β-hydroxy compound is, after the above step C, directly filter, then wash with tetrahydrofuran and combine the washings with the filtrate, add sodium perborate tetrahydrate to the filtrate, stir and fully react at room temperature, and separate and purify, namely have to. The beneficial effect is that the Y-type molecular sieve loaded with copper ions is used for the first time as a catalyst for preparing boron organic compounds, no additional ligand is needed, and the catalytic efficiency is high, the stability is good, and the non-toxic and green environmental protection is achieved.

Description

Catalytic Synthesis of Organoboron Compounds and β-hydroxyl Compounds by Supporting Copper Ion Y-type Molecular Sieves way of things

technical field

The invention belongs to the field of organic synthesis, and in particular relates to a method for preparing organoboron compounds and beta-hydroxy compounds by catalyzing the Y-type molecular sieves loaded with copper ions.

Background technique

Organoboron compounds are a class of important intermediates, which widely exist in the structure of natural products and drug molecules, and are also important synthons in organic synthesis. C-B bonds can be further converted into C-O, C-N bonds and C-C bonds. Compared with the traditional method using equivalent reagents, the strategy of direct boron addition to unsaturated carbonyl compounds under the action of catalysts is more direct and effective, and has received extensive attention in recent years. Most of the catalysts used in the literature are expensive transition metals, such as Rh, Ni, Pt, Pb, etc., which have high cost and are not suitable for actual production. In addition, there is also a method of using monovalent copper in the literature. Although the activity of the reaction is improved, the operation process is complicated, and harsh conditions such as strong alkali (potassium tert-butoxide, etc.), low temperature (-78 ° C), and strict anhydrous are required, These greatly limit the application of such methods in practical production. In comparison, bivalent copper is cheaper and more environmentally friendly, so the development of heterogeneous catalysts based on bivalent copper is the current research focus and difficulty in this field, and has important application value.

On the other hand, for heterogeneous catalysts, the choice of support is very important, and molecular sieves obtained by deacetylation of chitin, which are widely present in nature, are undoubtedly a good choice. Molecular sieves are not only cheap and easy to obtain, but also have excellent properties such as good biocompatibility, safety, and microbial degradability. So far, there is no relevant report on the catalytic preparation of organoboron compounds with copper ion-loaded molecular sieves.

In addition, the conversion of organoboron compounds to β-hydroxy compounds is an important application in industrial production, because β-hydroxy structures widely exist in natural products and drug molecular structures, so if a "one-pot" strategy can be adopted , firstly realize the boron addition of the substrate, and then do not need to separate and continuously convert it into β-hydroxy compounds, which will simplify the synthetic steps of natural products and has very important application value. In addition, organoboron compounds can be used as polymerization initiators, kerosene antioxidants, bactericides, anticancer drugs, etc., in addition to their wide application in organic synthesis.

SUMMARY OF THE INVENTION

The present invention provides a method for preparing organoboron compounds and β-hydroxyl compounds by loading copper ion Y-type molecular sieve microspheres, aiming to overcome the following deficiencies in the prior art at least to a certain extent: When a catalyst or an equivalent amount of reagent is used as a synthetic raw material, the cost is high and cannot be industrialized; when monovalent copper and nitrogen carbene ligands are used as catalysts, the operation process is complicated, requiring strong base (potassium tert-butoxide, etc.), low temperature (-78 ℃) , strict conditions such as anhydrous, also cause high production cost; if the existing β-hydroxy compound is prepared with an organoboron compound as a starting point, it means that it needs to be separated and purified from the reaction product after synthesizing the organoboron compound There is no continuous production, so the process route is complicated and the production efficiency is low.

The technical scheme that the present invention solves the above-mentioned technical problem is as follows: the method for preparing organoboron compound catalyzed by the supported copper ion Y-type molecular sieve, it comprises the following steps:

A. In the reaction vessel, add the loaded copper ion Y-type molecular sieve, tetrahydrofuran and water, fully stir at room temperature to obtain a mixed solution, and the ratio of the amount of the copper ion loaded by the loaded copper ion Y-type molecular sieve to the amount of water is 0.002 to 0.003 mmol: 1mL, the volume ratio of tetrahydrofuran and water is 0.5～1:1;

B. add α,β-unsaturated carbonyl compound I and biboronic acid pinacol ester to the described mixed solution obtained in step A, wherein, the consumption of α,β-unsaturated carbonyl compound I and water in the mixed solution The ratio is 0.15～0.25mmol:1mL, and the ratio of the amount of pinacol biborate to α,β-unsaturated carbonyl compound I is 1.0～2.0:1;

C. Stir the reaction at room temperature, and the reaction time is 10～16h;

D. after the reaction finishes, separate and purify to obtain organoboron compound II;

The chemical reaction equation is as follows:

Wherein R ¹ is phenone, p-methylphenone, p-methoxyphenone, p-fluorophenone, acetyl or pivaloyl; R ² is phenyl, p-methylphenyl, p-methyl Oxyphenyl, p-fluorophenyl, p-chlorophenyl, p-bromophenyl, p-trifluoromethylphenyl, m-bromophenyl, m-chlorophenyl, 2-thienyl, 2-naphthyl or 3- Allenylphenyl.

On the basis of the above technical solutions, the present invention can also have the following further specific options.

Specifically, the loading amount of copper ions in the Y-type molecular sieve that supports copper ions in A is 5-10 wt %. The preparation method of the supported copper ion Y-type molecular sieve is the prior art, and can be carried out with reference to the literature, such as can be prepared by the following method: (1) preparation concentration is the copper sulfate solution of 1mol/L. (2) Weigh 10g Y molecular sieve (Na type), add it to the beaker, then add 200mL copper sulfate solution, stir for 5 minutes, start heating after mixing evenly, start timing when the temperature rises to 80°C, and react for 8h. (3) Just hot filter, and then continue to add 200 mL of copper sulfate solution to the solid to repeat the operation of (2). (4) The turbid liquid was filtered, and the solid was washed with water several times until it was detected that the filtrate did not contain Cu(II) ions. (5) Dry the blue solid at 80°C for 12h. (6) Program the temperature of the dried solid sample (1°C/min) to 500°C for 3 hours under the condition of nitrogen flow, and then take out the sample after dropping to room temperature. The whole process needs to be protected by nitrogen. Finally, the copper ion-loaded Y-type molecular sieve (Y-zeolite@Cu(II)) is obtained. The divalent copper salt used is at least one of copper hydroxide, copper oxide, copper cyanide, copper sulfate, copper chloride, copper fluoride, copper bromide and basic copper carbonate. Copper sulfate is preferably used.

Specifically, in step A, the loading amount of copper ions in the Y-type molecular sieve loaded with copper ions is 5 to 10 wt %.

Specifically, the reaction temperature in step C is 0-30°C. Preferably, it is 20-25°C.

Preferably, the ratio of the amount of the biboronic acid pinacol ester reagent in B to the substance of the α,β-unsaturated carbonyl compound I is 1.2:1.

Specifically, the specific steps of separation and purification in D are as follows: after the reaction is completed, filter and wash with ethyl acetate, then extract with ethyl acetate, after separating the organic phase, dry with anhydrous sodium sulfate, filter, and remove the solvent by rotary evaporation , and the residue was separated and purified by column chromatography with a mixed solvent of ethyl acetate and petroleum ether.

The present invention also provides the method for the catalyzed preparation of β-hydroxy compound by the supported copper ion Y-type molecular sieve, which comprises the steps:

A. In the reaction vessel, add the loaded copper ion Y-type molecular sieve, tetrahydrofuran and water, and fully stir at room temperature to obtain a mixed solution. The amount ratio of the copper ion supported by the loaded copper ion Y-type molecular sieve to water is 0.01～0.015mmol: 1mL, and the tetrahydrofuran The volume ratio to water is 0.5 to 1:1;

B. add α,β-unsaturated carbonyl compound I and biboronic acid pinacol ester to the described mixed solution obtained in step A, wherein the difference between α,β-unsaturated carbonyl compound I and the amount of water in the mixed solution The ratio is 0.15～0.25mmol: 1mL, and the ratio of the amount of pinacol biborate to α,β-unsaturated carbonyl compound I is 1.0～2.0:1;

C. The reaction is stirred at room temperature, and the reaction time is 10 to 16 h to obtain a reaction solution containing the organoboron compound II;

D. After the reaction, the reaction solution was filtered, the filter cake was washed with tetrahydrofuran, the washing solution was combined with the filtrate, sodium perborate tetrahydrate was added to the combined filtrate, and the reaction was stirred at room temperature for 4 to 8 hours. The ratio of the amount of sodium to the α, β-unsaturated carbonyl compound I added in step B is 2.0 to 4.0:1, and the volume ratio of the tetrahydrofuran used for washing in step D to the water added in step A is 1.5 to 2 :1;

E. after the reaction finishes, separate and purify to obtain β-hydroxy compound III;

The chemical reaction equation is as follows:

Wherein R ¹ is phenone, p-methyl phenone, p-methoxyphenone, p-fluorophenone, acetyl, pivaloyl; R ² is phenyl, p-methylphenyl, p-methyl Oxyphenyl, p-fluorophenyl, p-chlorophenyl, p-bromophenyl, p-trifluoromethylphenyl, m-bromophenyl, m-chlorophenyl, 2-thienyl, 2-naphthyl, 3- Allenylphenyl.

On the basis of the above technical solutions, the present invention can also have the following further specific options.

Specifically, the loading amount of copper ions in the Y-type molecular sieve that supports copper ions in A is 5-10 wt %.

Specifically, the reaction temperature in step C is 0-30°C. Preferably, it is 20-25°C.

Preferably, the ratio of the amount of the biboronic acid pinacol ester reagent in B to the substance of the α,β-unsaturated carbonyl compound I is 1.2:1.

Specifically, the ratio of the substance amount of the sodium perborate tetrahydrate added in D to the α,β-unsaturated carbonyl compound (I) added in B is 2.0-4.0: 1, and the tetrahydrofuran used for washing in D and in A The volume ratio of added water is 1.5-2:1.

Specifically, the specific steps of separation and purification in E are as follows: after the reaction is completed, filter and wash with ethyl acetate, then extract with ethyl acetate, after separating the organic phase, dry with anhydrous sodium sulfate, filter, and remove the solvent by rotary evaporation , and the residue was separated and purified by column chromatography with a mixed solvent of ethyl acetate and petroleum ether.

Compared with the prior art, the beneficial effects of the present invention are:

1. the method provided by the invention uses the Y-type molecular sieve of supported copper ions as the catalyst for preparing boron organic compounds for the first time, not only the carrier skeleton or the ligand of copper ions, with respect to the traditional adsorption load, the copper ions of the present application and the carrier skeleton The combination is more stable, and at the same time does not need to add additional complex ligands, high catalytic efficiency, good stability, non-toxicity, good biocompatibility, green environmental protection;

2. The catalyst dosage and reaction time of the method are greatly reduced compared with the similar reactions in the prior art, and only a lower catalyst dosage is required to achieve a higher conversion rate of the reactants;

3. The method has mild reaction conditions, can react at room temperature, does not need an anhydrous and oxygen-free reaction environment, and is simple and easy to operate;

4. The method has wide applicability and can be used for the boron addition of various types of α, β-unsaturated carbonyl compounds, and the corresponding organoboron compounds and β-hydroxy compounds have been successfully prepared.

5. The strategy of "one-pot method" can be adopted in this method, and the β-hydroxy compound containing carbonyl group is directly prepared from the starting material through continuous boron addition reaction and oxidation reaction.

6. The molecular sieve catalytic material used in the method can be recycled and reused for more than 7 times, and the reactivity will not be significantly reduced, and the separation of the catalytic material can be realized by a simple filtering operation, which is more suitable for industrialized large-scale production.

Detailed ways

The technical solutions of the present invention are described in further detail below in conjunction with specific embodiments, and the examples are only used to explain the present invention, and are not intended to limit the scope of the present invention.

The starting material is α,β-unsaturated carbonyl compound I, which is prepared by the method provided by the present invention to obtain organoboron compound II, which is then converted into β-hydroxy compound III.

其中R¹为 苯酮基、对甲基苯酮基、对甲氧基苯酮基、对氟苯酮基、乙酰基、新戊酰基、 氰基、间甲基苯酮基；R²为苯基、对甲基苯基、对甲氧基苯基、对氟苯基、 对氯苯基、对溴苯基、对三氟甲基苯基、间溴苯基、间氯苯基、2-噻吩基、 2-萘基、3-丙烯基苯基。The chemical formula of α,β-unsaturated carbonyl compound I in the following examples is

Wherein R ¹ is phenone group, p-methyl phenone group, p-methoxyphenone group, p-fluorophenone group, acetyl group, pivaloyl group, cyano group, m-methyl phenone group; R ² is benzene phenyl, p-methylphenyl, p-methoxyphenyl, p-fluorophenyl, p-chlorophenyl, p-bromophenyl, p-trifluoromethylphenyl, m-bromophenyl, m-chlorophenyl, 2- thienyl, 2-naphthyl, 3-propenylphenyl.

In the following examples, preferably, R ¹ of α,β-unsaturated carbonyl compound I-1 is phenone, R ² is phenyl; R ¹ of I-2 is phenone, and R ² is p-methyl Phenyl; R ¹ of I-3 is phenone, R ² is p-methoxyphenyl; R ¹ of I-4 is p-methyl phenone, R ² is phenyl; R ¹ of I-5 For p-methoxyphenone group, R ² is phenyl; R ¹ of I-6 is p-fluorophenone group, R ² is phenyl; R ¹ of I-7 is phenone group, R ² is p-fluorine Phenyl; R ¹ of I-8 is phenone, R ² is p-chlorophenyl; R ¹ of I-9 is phenone, R ² is p-bromophenyl; R ¹ of I-10 is acetyl , R ² is phenyl; R ¹ of I-11 is pivaloyl, and R ² is phenyl; R ¹ of I-12 is phenone, and R ² is 2-thienyl; R ¹ of I-13 is p-Fluorophenone group, R ² is 2-thienyl; R ¹ of I-14 is phenone group, R ² is p-trifluoromethyl phenyl; R ¹ of I-15 is p-methoxyphenone group , R ² is p-methoxyphenyl; R ¹ of I-16 is p-methyl phenone, R ² is p-fluorophenyl; R ¹ of I-17 is p-methyl phenone, R ² is p-bromophenyl; R ¹ of I-18 is p-fluorobenzophenone, R ² is p-bromophenyl; R ¹ of I-19 is methylphenone, R ² is phenyl; I-20 R ¹ is p-methoxyphenone group, R ² is chlorophenyl; R ¹ of I-21 is phenone group, R ² is 2-naphthyl; R ¹ of I-22 is acetyl group, R ² It is p-methoxyphenyl; R ¹ of I-23 is phenone group, and R ² is 3-propenyl phenyl group.

The chemical structural formulas corresponding to the organic boron compound II in the following examples are as follows:

The chemical structural formula corresponding to β-hydroxy compound III in the following examples is as follows:

The methods used in the following examples are conventional methods in the art without special instructions, and the medicines used are commercially available products without special instructions.

Example 1:

A preparation method of organoboron compound II-1, the steps are:

A. In a 2.5mL reaction tube, add 0.002 mmol of Y-type molecular sieve (Y-zeolite@CuSO ₄ ) loaded with copper ions (in terms of the amount of loaded copper ions, the loading amount is 5-10wt%, the same below), and add 1.0 mL tetrahydrofuran and 1.0 mL water were stirred at room temperature (20-25°C, the same below) for 1 hour;

B. In the above system, α,β-unsaturated carbonyl compound I-1 (41.6 mg, 0.2 mmol) and biboronic acid pinacol ester (B ₂ (pin) ₂ ) (60.9 mg, 2.4 mmol) were successively added successively respectively. );

C. the whole reaction system was stirred and reacted at room temperature, and the reaction time was 12 hours;

D. After the reaction, the entire reaction system was filtered, washed with 10 mL of ethyl acetate, and then extracted with ethyl acetate (3×10 mL). After separating the organic phase, it was dried with anhydrous Na ₂ SO ₄ , filtered, and removed by rotary evaporation. solvent. The residue was purified by ethyl acetate/petroleum ether mixed solvent=9:1 column chromatography to obtain II-1 pale yellow solid, 65.2 mg, yield 97%.

The H NMR and C spectra of the target product are shown below:

¹ H NMR (400MHz, Chloroform-d) δ8.00–7.93 (m, 2H), 7.52 (t, J=7.5Hz, 1H), 7.41 (t, J=7.8Hz, 2H), 7.32–7.23 (m ,4H),7.16-7.12(m,1H),3.54-3.51(m,1H),3.41-3.38(m,1H),1.26(s,6H),1.18(s,6H).

¹³ C NMR (100MHz, Chloroform-d) δ=202.4, 144.6, 139.4, 135.6, 131.2, 131.1, 131.0, 130.7, 128.3, 86.1, 46.0, 27.2, 27.1.

¹¹ B NMR (120MHz, Chloroform-d) δ32.6(s).

Example 2:

A preparation method of organoboron compound II-2, the steps are:

A. Add 0.002 mmol of Y-type molecular sieve (Y-zeolite@CuSO ₄ ) loaded with copper ions into a 2.5 mL reaction tube, and add 1.0 mL of tetrahydrofuran and 1.0 mL of water, and stir at room temperature (20-25° C., the same below) for 1 Hour;

B. To the above system, α, β-unsaturated carbonyl compound I-2 (47.7mg, 0.2mmol) and biboronic acid pinacol ester (B ₂ (pin) ₂ ) (60.9mg, 2.4 mmol) were successively added successively respectively. );

C. the whole reaction system was stirred and reacted at room temperature, and the reaction time was 12 hours;

D. After the reaction, the entire reaction system was filtered, washed with 10 mL of ethyl acetate, and then extracted with ethyl acetate (3×10 mL). After separating the organic phase, it was dried with anhydrous Na ₂ SO ₄ , filtered, and removed by rotary evaporation. solvent. The residue was purified by column chromatography with ethyl acetate/petroleum ether mixed solvent=9:1 to obtain II-2 pale yellow solid, 72.5 mg, yield 99%.

The H NMR and C spectra of the target product are shown below:

¹ H NMR(400MHz, Chloroform-d)δ8.00-7.92(m,2H),7.57-7.36(m,3H), 7.21(d,J=8.5Hz,2H),6.83(d,J=8.6Hz ,2H),3.76(s,3H),3.51-3.45(m,1H), 3.39-3.35(m,1H),2.74-2.70(m,1H),1.20-1.15(m,12H).

¹³ C NMR (100MHz, Chloroform-d) δ=199.8, 157.6, 136.8, 133.8, 132.8, 129.3, 128.5, 128.0, 113.9, 83.3, 55.2, 43.6, 24.6, 24.5.

¹¹ B NMR (120 MHz, Chloroform-d) δ 32.9 (s).

Example 3:

A kind of preparation method of organic boron compound II-3, its steps are:

A. Add 0.002 mmol of Y-type molecular sieve (Y-zeolite@CuSO ₄ ) loaded with copper ions into a 2.5 mL reaction tube, and add 1.0 mL of tetrahydrofuran and 1.0 mL of water, and stir at room temperature (20-25° C., the same below) for 1 Hour;

B. In the above system, α, β-unsaturated carbonyl compound I-3 (45.3 mg, 0.2 mmol) and biboronic acid pinacol ester (B ₂ (pin) ₂ ) (60.9 mg, 2.4 mmol) were successively added successively respectively. );

C. the whole reaction system was stirred and reacted at room temperature, and the reaction time was 12 hours;

D. After the reaction, the entire reaction system was filtered, washed with 10 mL of ethyl acetate, and then extracted with ethyl acetate (3×10 mL). After separating the organic phase, it was dried with anhydrous Na ₂ SO ₄ , filtered, and removed by rotary evaporation. solvent. The residue was purified by ethyl acetate/petroleum ether mixed solvent=9:1 column chromatography to obtain II-3 69.4 mg, yield 98%.

The H NMR and C spectra of the target product are shown below:

¹ H NMR (400MHz, Chloroform-d) δ8.03-7.85 (m, 2H), 7.53 (t, J=7.5Hz, 1H), 7.42 (t, J=7.8Hz, 2H), 7.31-7.20 (m ,2H),6.94(t,J＝8.8Hz,2H), 3.50-3.45(m,1H),3.40-3.36(m,1H),2.78-2.74(m,1H),1.23(s,6H), 1.16(s, 6H)

¹³ C NMR (100MHz, Chloroform-d) δ199.5, 161.9, 160.3, 137.6, 137.5, 136.7, 133.0, 129.7, 129.7, 128.5, 128.0, 115.3, 115.1, 83.5, 43.2, 24.6, 24.5.

¹¹ B NMR (120MHz, Chloroform-d) δ33.3(s).

Example 4:

A preparation method of β-hydroxy compound III-1, the steps are:

A. Add 0.002 mmol of Y-type molecular sieve (Y-zeolite@CuSO ₄ ) loaded with copper ions into a 2.5 mL reaction tube, and add 1.0 mL of tetrahydrofuran and 1.0 mL of water, and stir at room temperature (20-25° C., the same below) for 1 Hour;

B. In the above system, α, β-unsaturated carbonyl compound I-1 (41.7 mg, 0.2 mmol) and biboronic acid pinacol ester (B ₂ (pin) ₂ ) (60.9 mg, 2.4 mmol) were successively added successively respectively. );

C. the whole reaction system was stirred and reacted at room temperature, and the reaction time was 12 hours;

D. After the reaction is completed, the entire reaction system is filtered, and after the reaction is completed, the entire reaction system is filtered and washed with 2 mL of tetrahydrofuran. To the residue was directly added 244 mg of sodium perborate tetrahydrate, and the whole system was stirred at room temperature for 4 hours.

E. After the reaction, the entire reaction system was filtered, washed with 10 mL of ethyl acetate, and then extracted with ethyl acetate (3×10 mL). After separating the organic phase, it was dried with anhydrous Na ₂ SO ₄ , filtered, and removed by rotary evaporation. solvent. The residue was purified by column chromatography with ethyl acetate/petroleum ether mixed solvent=4:1 to obtain III-1 colorless oily liquid, 43.9 mg, yield 97%.

The H NMR and C spectra of the target product are shown below:

¹ H NMR (400MHz); δ=7.97 (d, J=7.2Hz, 2H), 7.61-7.57 (m, 1H), 7.49-7.44 (m, 4H), 7.41 (t, J=7.5Hz, 2H) ,7.33-7.29(m,1H),5.37(t,J＝6.1Hz,1H),3.65(br,1H),3.39-3.37(m,2H).

¹³ C NMR (100 MHz); δ=200.1, 142.9, 136.4, 133.6, 133.6, 128.7, 128.5, 128.1, 127.6, 125.7, 70.0, 47.3.

Example 5:

A preparation method of β-hydroxy compound III-2, the steps are:

A. Add 0.002 mmol of Y-type molecular sieve (Y-zeolite@CuSO ₄ ) loaded with copper ions into a 2.5 mL reaction tube, and add 1.0 mL of tetrahydrofuran and 1.0 mL of water, and stir at room temperature (20-25° C., the same below) for 1 Hour;

B. To the above system, α, β-unsaturated carbonyl compound I-2 (47.7mg, 0.2mmol) and biboronic acid pinacol ester (B ₂ (pin) ₂ ) (60.9mg, 2.4 mmol) were successively added successively respectively. );

C. the whole reaction system was stirred and reacted at room temperature, and the reaction time was 12 hours;

D. After the reaction is completed, the entire reaction system is filtered, and after the reaction is completed, the entire reaction system is filtered and washed with 2 mL of tetrahydrofuran. To the residue was directly added 244 mg of sodium perborate tetrahydrate, and the whole system was stirred at room temperature for 4 hours.

E. After the reaction, the entire reaction system was filtered, washed with 10 mL of ethyl acetate, and then extracted with ethyl acetate (3×10 mL). After separating the organic phase, it was dried with anhydrous Na ₂ SO ₄ , filtered, and removed by rotary evaporation. solvent. The residue was purified by column chromatography with ethyl acetate/petroleum ether mixed solvent=4:1 to obtain III-2 as a white solid, 45.2 mg, yield 94%.

The nuclear hydrogen and carbon spectra of the target product are shown below:

¹ H NMR (400 MHz); δ=7.97 (d, J=7.0 Hz, 2H), 7.61-7.57 (m, 1H), 7.49 (t, J=7.7 Hz, 2H), 7.21 (d, J=7.9 Hz) ,2H),5.34-5.30(m,1H),3.60(s,1H), 3.43-3.32(m,2H),2.37(s,3H).

magnetic

¹³ C NMR (100 MHz); δ=200.1, 140.0, 137.3, 136.5, 133.5, 129.2, 128.6, 128.1, 125.6, 77.3, 77.0, 76.7, 69.8, 47.3, 21.1.

Example 6:

A preparation method of β-hydroxy compound III-3, the steps are:

A. Add 0.002 mmol of Y-type molecular sieve (Y-zeolite@CuSO ₄ ) loaded with copper ions into a 2.5 mL reaction tube, and add 1.0 mL of tetrahydrofuran and 1.0 mL of water, and stir at room temperature (20-25° C., the same below) for 1 Hour;

B. In the above system, α, β-unsaturated carbonyl compound I-3 (45.3 mg, 0.2 mmol) and biboronic acid pinacol ester (B ₂ (pin) ₂ ) (60.9 mg, 2.4 mmol) were successively added successively respectively. );

C. the whole reaction system was stirred and reacted at room temperature, and the reaction time was 12 hours;

D. After the reaction is completed, the entire reaction system is filtered, and after the reaction is completed, the entire reaction system is filtered and washed with 2 mL of tetrahydrofuran. To the residue was directly added 244 mg of sodium perborate tetrahydrate, and the whole system was stirred at room temperature for 4 hours.

E. After the reaction, the entire reaction system was filtered, washed with 10 mL of ethyl acetate, and then extracted with ethyl acetate (3×10 mL). After separating the organic phase, it was dried with anhydrous Na ₂ SO ₄ , filtered, and removed by rotary evaporation. solvent. The residue was purified by column chromatography with ethyl acetate/petroleum ether mixed solvent=4:1 to obtain III-3 as a colorless oily liquid, 42.5 mg, yield 83%.

The H NMR and C spectra of the target product are shown below:

¹ H NMR (400MHz); δ=7.97-7.94 (m, 2H), 7.61-7.57 (m, 1H), 7.49-7.45 (m, 2H), 7.38-7.35 (m, 2H), 6.92-6.90 (m ,2H),5.31(dd,J=7.6,4.6Hz,1H), 3.81(s,1H),3.38-3.35(m,2H).

¹³ C NMR (100 MHz); δ=200.3, 159.1, 136.6, 135.1, 133.6, 128.7, 128.1, 127.0, 113.9, 77.3, 77.0, 76.7, 69.7, 55.3, 47.3.

Example 7:

A preparation method of β-hydroxy compound III-4, the steps are:

A. Add 0.002 mmol of Y-type molecular sieve (Y-zeolite@CuSO ₄ ) loaded with copper ions into a 2.5 mL reaction tube, and add 1.0 mL of tetrahydrofuran and 1.0 mL of water, and stir at room temperature (20-25° C., the same below) for 1 Hour;

B. In the above system, α, β-unsaturated carbonyl compound I-4 (44.5mg, 0.2mmol) and biboronic acid pinacol ester (B ₂ (pin) ₂ ) (60.9mg, 2.4 mmol) were successively added successively respectively. );

C. the whole reaction system was stirred and reacted at room temperature, and the reaction time was 12 hours;

D. After the reaction is completed, the entire reaction system is filtered, and after the reaction is completed, the entire reaction system is filtered and washed with 2 mL of tetrahydrofuran. To the residue was directly added 244 mg of sodium perborate tetrahydrate, and the whole system was stirred at room temperature for 4 hours.

E. After the reaction, the entire reaction system was filtered, washed with 10 mL of ethyl acetate, and then extracted with ethyl acetate (3×10 mL). After separating the organic phase, it was dried with anhydrous Na ₂ SO ₄ , filtered, and removed by rotary evaporation. solvent. The residue was purified by column chromatography with ethyl acetate/petroleum ether mixed solvent=4:1 to obtain III-4 as a white solid, 43.3 mg, yield 90%.

The H NMR and C spectra of the target product are shown below:

¹ H NMR (400MHz); δ = 7.84 (d, J = 8.3 Hz, 2H), 7.42 (d, J = 7.2 Hz, 2H), 7.37 (t, J = 7.4 Hz, 2H), 7.30 (d, J =7.2Hz,1H),7.26-7.23(m,2H),5.33-5.30(m,1H),3.71(s,1H),3.36-3.27(m,2H),2.39(s,3H).

¹³ C NMR (100 MHz); δ=199.8, 144.6, 142.9, 134.0, 129.3, 128.5, 128.2, 127.6, 125.7, 77.3, 77.0, 76.7, 70.0, 47.2, 21.7.

Example 8:

A preparation method of β-hydroxy compound III-5, the steps are:

A. Add 0.002 mmol of Y-type molecular sieve (Y-zeolite@CuSO ₄ ) loaded with copper ions into a 2.5 mL reaction tube, and add 1.0 mL of tetrahydrofuran and 1.0 mL of water, and stir at room temperature (20-25° C., the same below) for 1 Hour;

B. In the above system, α,β-unsaturated carbonyl compound I-5 (47.7mg, 0.2mmol) and biboronic acid pinacol ester (B ₂ (pin) ₂ ) (60.9mg, 2.4 mmol) were successively added successively respectively. );

C. the whole reaction system was stirred and reacted at room temperature, and the reaction time was 12 hours;

D. After the reaction is completed, the entire reaction system is filtered, and after the reaction is completed, the entire reaction system is filtered and washed with 2 mL of tetrahydrofuran. To the residue was directly added 244 mg of sodium perborate tetrahydrate, and the whole system was stirred at room temperature for 4 hours.

E. After the reaction, the entire reaction system was filtered, washed with 10 mL of ethyl acetate, and then extracted with ethyl acetate (3×10 mL). After separating the organic phase, it was dried with anhydrous Na ₂ SO ₄ , filtered, and removed by rotary evaporation. solvent. The residue was purified by column chromatography with ethyl acetate/petroleum ether mixed solvent=4:1 to obtain III-5 as a white solid, 44.1 mg, yield 86%.

The H NMR and C spectra of the target product are shown below:

¹ H NMR (400 MHz); δ=7.95 (d, J=8.8 Hz, 2H), 7.45 (d, J=6.7 Hz, 2H), 7.40 (t, J=7.3 Hz, 2H), 7.32 (t, J =7.2Hz,1H),6.94(d,J=8.8Hz,2H),5.34(dd,J=8.3,3.8Hz,1H),3.87(s,3H),3.79(s,1H),3.36-3.26 (m,2H).

¹³ C NMR (100 MHz); δ=198.8, 163.9, 143.0, 130.5, 129.6, 128.5, 127.6, 125.7, 113.8, 77.3, 77.0, 76.7, 70.1, 55.5, 46.9.

Example 9:

A preparation method of β-hydroxy compound III-6, the steps are:

A. In a 2.5mL reaction tube, add copper ion-loaded Y-type molecular sieve (Y-zeolite@CuSO ₄ ), calculated as Cu ion 0.002mmol, and add 1.0mL of tetrahydrofuran and 1.0mL of water, at room temperature (20-25°C, the same as below) ) under stirring for 1 hour;

B. In the above system, α,β-unsaturated carbonyl compound I-6 (45.3 mg, 0.2 mmol) and biboronic acid pinacol ester (B ₂ (pin) ₂ ) (60.9 mg, 2.4 mmol) were successively added successively respectively. );

C. the whole reaction system was stirred and reacted at room temperature, and the reaction time was 12 hours;

D. After the reaction is completed, the entire reaction system is filtered, and after the reaction is completed, the entire reaction system is filtered and washed with 2 mL of tetrahydrofuran. To the residue was directly added 244 mg of sodium perborate tetrahydrate, and the whole system was stirred at room temperature for 4 hours.

E. After the reaction, the entire reaction system was filtered, washed with 10 mL of ethyl acetate, and then extracted with ethyl acetate (3×10 mL). After separating the organic phase, it was dried with anhydrous Na ₂ SO ₄ , filtered, and removed by rotary evaporation. solvent. The residue was purified by column chromatography with ethyl acetate/petroleum ether mixed solvent=4:1 to obtain III-6 colorless oily liquid, 41.0 mg, yield 84%.

The H NMR and C spectra of the target product are shown below:

¹ H NMR (400 MHz); δ=8.00 (dd, J=8.9 Hz, 5.4 Hz, 2H), 7.44 (d, J=6.8 Hz, 2H), 7.40 (t, J=7.4 Hz, 2H), 7.32 ( t,J＝7.1Hz,1H),7.15(t,J＝8.6Hz,2H), 5.36(dd,J＝8.6,3.6Hz,1H),3.55(s,1H),3.40-3.28(m,2H) ).

¹³ C NMR (100 MHz); δ=198.4, 167.3, 164.7, 142.8, 132.99, 132.96, 130.9, 130.8, 128.6, 127.7, 125.7, 115.9, 115.7, 77.3, 77.0, 76.7, 70.0, 47.3.

Example 10:

A preparation method of β-hydroxy compound III-7, the steps are:

A. Add 0.002 mmol of Y-type molecular sieve (Y-zeolite@CuSO ₄ ) loaded with copper ions into a 2.5 mL reaction tube, and add 1.0 mL of tetrahydrofuran and 1.0 mL of water, and stir at room temperature (20-25° C., the same below) for 1 Hour;

B. In the above system, α, β-unsaturated carbonyl compound I-7 (44.5mg, 0.2mmol) and biboronic acid pinacol ester (B ₂ (pin) ₂ ) (60.9mg, 2.4 mmol) were successively added successively respectively. );

C. the whole reaction system was stirred and reacted at room temperature, and the reaction time was 12 hours;

D. After the reaction is completed, the entire reaction system is filtered, and after the reaction is completed, the entire reaction system is filtered and washed with 2 mL of tetrahydrofuran. To the residue was directly added 244 mg of sodium perborate tetrahydrate, and the whole system was stirred at room temperature for 4 hours.

E. After the reaction, the entire reaction system was filtered, washed with 10 mL of ethyl acetate, and then extracted with ethyl acetate (3×10 mL). After separating the organic phase, it was dried with anhydrous Na ₂ SO ₄ , filtered, and removed by rotary evaporation. solvent. The residue was purified by column chromatography with ethyl acetate/petroleum ether mixed solvent=4:1 to obtain III-7 as a colorless oily liquid, 45.4 mg, yield 93%.

The H NMR and C spectra of the target product are shown below:

¹ H NMR (400MHz); δ=7.96-7.94 (m, 2H), 7.61-7.57 (m, 1H), 7.49-7.39 (m, 5H), 7.08 (t, J=8.7Hz, 1H), 5.34 ( t, J=6.1Hz, 1H), 3.72(br, 1H), 3.35(d, J=6.1Hz, 2H).

¹³ C NMR (100 MHz); δ=200.0, 163.4, 160.9, 138.7, 138.6, 136.4, 133.7, 128.7, 128.1, 127.44, 127.36, 115.4, 115.2, 69.4, 47.3.

Example 11:

A preparation method of β-hydroxy compound III-8, the steps are:

A. Add 0.002 mmol of Y-type molecular sieve (Y-zeolite@CuSO ₄ ) loaded with copper ions into a 2.5 mL reaction tube, and add 1.0 mL of tetrahydrofuran and 1.0 mL of water, and stir at room temperature (20-25° C., the same below) for 1 Hour;

B. In the above system, α,β-unsaturated carbonyl compound I-8 (48.5mg, 0.2mmol) and biboronic acid pinacol ester (B ₂ (pin) ₂ ) (60.9mg, 2.4 mmol) were successively added successively respectively. );

C. the whole reaction system was stirred and reacted at room temperature, and the reaction time was 12 hours;

D. After the reaction is completed, the entire reaction system is filtered, and after the reaction is completed, the entire reaction system is filtered and washed with 2 mL of tetrahydrofuran. To the residue was directly added 244 mg of sodium perborate tetrahydrate, and the whole system was stirred at room temperature for 4 hours.

E. After the reaction, the entire reaction system was filtered, washed with 10 mL of ethyl acetate, and then extracted with ethyl acetate (3×10 mL). After separating the organic phase, it was dried with anhydrous Na ₂ SO ₄ , filtered, and removed by rotary evaporation. solvent. The residue was purified by column chromatography with ethyl acetate/petroleum ether mixed solvent=4:1 to obtain III-8 white solid, 43.8 mg, yield 84%.

The H NMR and C spectra of the target product are shown below:

¹ H NMR (400MHz); δ=7.96 (d, J=6.9Hz, 2H), 7.62 (t, J=7.4Hz, 1H), 7.50 (t, J=7.7Hz, 2H), 7.39-7.34 (m ,4H),5.34(dd,J=7.8,4.3Hz,1H),3.66(s,1H),3.35-3.33(m,2H).

¹³ C NMR (100 MHz); δ=200.0, 141.4, 136.4, 133.8, 133.3, 128.74, 128.68, 128.1, 127.1, 77.3, 77.0, 76.7, 69.4, 47.2.

Example 12:

A preparation method of β-hydroxy compound III-9, the steps are:

A. Add copper ion-loaded Y-type molecular sieve (Y-zeolite@CuSO ₄ ) into a 2.5mL reaction tube

0.002 mmol, and 1.0 mL of tetrahydrofuran and 1.0 mL of water were added, and stirred for 1 hour at room temperature (20-25 ° C, the same below);

B. In the above system, α, β-unsaturated carbonyl compound I-9 (57.4 mg, 0.2 mmol) and biboronic acid pinacol ester (B ₂ (pin) ₂ ) (60.9 mg, 2.4 mmol) were successively added successively respectively. );

C. the whole reaction system was stirred and reacted at room temperature, and the reaction time was 12 hours;

D. After the reaction is completed, the entire reaction system is filtered, and after the reaction is completed, the entire reaction system is filtered and washed with 2 mL of tetrahydrofuran. To the residue was directly added 244 mg of sodium perborate tetrahydrate, and the whole system was stirred at room temperature for 4 hours.

E. After the reaction, the entire reaction system was filtered, washed with 10 mL of ethyl acetate, and then extracted with ethyl acetate (3×10 mL). After separating the organic phase, it was dried with anhydrous Na ₂ SO ₄ , filtered, and removed by rotary evaporation. solvent. The residue was purified by column chromatography with ethyl acetate/petroleum ether mixed solvent=4:1 to obtain III-9 as a white solid, 40.9 mg, yield 67%.

The H NMR and C spectra of the target product are shown below:

¹ H NMR (400MHz); δ=7.95 (d, J=7.0Hz, 2H), 7.62 (t, J=7.4Hz, 1H), 7.51-7.45 (m, 4H), 7.33 (d, J=8.4Hz) ,2H),5.32(dd,J＝7.4,4.8Hz,1H),3.68(s,1H),3.38-3.28(m,2H).

¹³ C NMR (100 MHz); δ=199.9, 141.9, 136.3, 133.8, 131.6, 128.7, 128.1, 127.5, 121.4, 77.3, 77.0, 76.6, 69.4, 47.2.

Example 13:

A preparation method of β-hydroxy compound III-10, the steps are:

A. Add 0.002 mmol of Y-type molecular sieve (Y-zeolite@CuSO ₄ ) loaded with copper ions into a 2.5 mL reaction tube, and add 1.0 mL of tetrahydrofuran and 1.0 mL of water, and stir at room temperature (20-25° C., the same below) for 1 Hour;

B. In the above system, α,β-unsaturated carbonyl compound I-10 (29.2 mg, 0.2 mmol) and biboronic acid pinacol ester (B ₂ (pin) ₂ ) (60.9 mg, 2.4 mmol) were successively added successively. );

C. the whole reaction system was stirred and reacted at room temperature, and the reaction time was 12 hours;

D. After the reaction is completed, the entire reaction system is filtered, and after the reaction is completed, the entire reaction system is filtered and washed with 2 mL of tetrahydrofuran. To the residue was directly added 244 mg of sodium perborate tetrahydrate, and the whole system was stirred at room temperature for 4 hours.

E. After the reaction, the entire reaction system was filtered, washed with 10 mL of ethyl acetate, and then extracted with ethyl acetate (3×10 mL). After separating the organic phase, it was dried with anhydrous Na ₂ SO ₄ , filtered, and removed by rotary evaporation. solvent. The residue was purified by column chromatography with ethyl acetate/petroleum ether mixed solvent=4:1 to obtain III-10 pale yellow oily liquid, 26.9 mg, yield 82%.

The H NMR and C spectra of the target product are shown below:

¹ H NMR (400MHz); δ=7.36 (d, J=4.5Hz, 4H), 7.30-7.27 (m, 1H), 5.17-5.13 (m, 1H), 3.39 (s, 1H), 2.93-2.79 ( m, 2H), 2.79(s, 3H).

¹³ C NMR (100 MHz); δ=209.1, 142.7, 128.5, 127.6, 125.6, 77.3, 77.0, 76.7, 69.8, 51.9, 30.7.

Example 14:

A preparation method of β-hydroxy compound III-11, the steps are:

A. Add 0.002 mmol of Y-type molecular sieve (Y-zeolite@CuSO ₄ ) loaded with copper ions into a 2.5 mL reaction tube, and add 1.0 mL of tetrahydrofuran and 1.0 mL of water, and stir at room temperature (20-25° C., the same below) for 1 Hour;

B. In the above system, α, β-unsaturated carbonyl compound I-11 (37.7 mg, 0.2 mmol) and biboronic acid pinacol ester (B ₂ (pin) ₂ ) (60.9 mg, 2.4 mmol) were successively added successively. );

C. the whole reaction system was stirred and reacted at room temperature, and the reaction time was 12 hours;

D. After the reaction is completed, the entire reaction system is filtered, and after the reaction is completed, the entire reaction system is filtered and washed with 2 mL of tetrahydrofuran. To the residue was directly added 244 mg of sodium perborate tetrahydrate, and the whole system was stirred at room temperature for 4 hours.

E. After the reaction, the entire reaction system was filtered, washed with 10 mL of ethyl acetate, and then extracted with ethyl acetate (3×10 mL). After separating the organic phase, it was dried with anhydrous Na ₂ SO ₄ , filtered, and removed by rotary evaporation. solvent. The residue was purified by column chromatography with ethyl acetate/petroleum ether mixed solvent=4:1 to obtain III-11 pale yellow oily liquid, 29.3 mg, yield 71%.

The H NMR and C spectra of the target product are shown below:

¹ H NMR (400MHz); δ=7.38-7.28(m,5H), 5.15-5.11(m,1H), 3.64(s,1H), 2.89-2.87(m,2H), 1.13(s,9H).

¹³ C NMR (100 MHz); δ=216.8, 143.0, 128.4, 127.5, 125.6, 77.3, 77.0, 76.7, 70.0, 45.4, 44.3, 26.1, 30.7.

Example 15:

A preparation method of β-hydroxy compound III-12, the steps are:

A. Add 0.002 mmol of Y-type molecular sieve (Y-zeolite@CuSO ₄ ) loaded with copper ions into a 2.5 mL reaction tube, and add 1.0 mL of tetrahydrofuran and 1.0 mL of water, and stir at room temperature (20-25° C., the same below) for 1 Hour;

B. In the above system, α,β-unsaturated carbonyl compound I-12 (42.9 mg, 0.2 mmol) and biboronic acid pinacol ester (B ₂ (pin) ₂ ) (60.9 mg, 2.4 mmol) were successively added successively respectively. );

C. the whole reaction system was stirred and reacted at room temperature, and the reaction time was 12 hours;

D. After the reaction is completed, the entire reaction system is filtered, and after the reaction is completed, the entire reaction system is filtered and washed with 2 mL of tetrahydrofuran. To the residue was directly added 244 mg of sodium perborate tetrahydrate, and the whole system was stirred at room temperature for 4 hours.

E. After the reaction, the entire reaction system was filtered, washed with 10 mL of ethyl acetate, and then extracted with ethyl acetate (3×10 mL). After separating the organic phase, it was dried with anhydrous Na ₂ SO ₄ , filtered, and removed by rotary evaporation. solvent. The residue was purified by column chromatography with ethyl acetate/petroleum ether mixed solvent=4:1 to obtain III-12 as a colorless oily liquid, 37.2 mg, yield 80%.

The H NMR and C spectra of the target product are shown below:

¹ H NMR (400 MHz); δ=7.97 (d, J=8.1 Hz, 2H), 7.61-7.57 (m, 1H), 7.49-7.45 (m, 2H), 7.26-7.25 (m, 1H), 7.03- 6.97(m,2H),5.61-5.57(m,1H),3.83(s,1H),3.51-3.48(m,2H).

¹³ C NMR (100 MHz); δ=199.5, 146.6, 136.3, 133.7, 128.7, 128.1, 126.6, 124.6, 123.5, 77.3, 70.0, 76.7, 66.4, 47.1.

Example 16:

A preparation method of β-hydroxy compound III-13, the steps are:

A. Add 0.002 mmol of Y-type molecular sieve (Y-zeolite@CuSO ₄ ) loaded with copper ions into a 2.5 mL reaction tube, and add 1.0 mL of tetrahydrofuran and 1.0 mL of water, and stir at room temperature (20-25° C., the same below) for 1 Hour;

B. In the above system, α, β-unsaturated carbonyl compound I-13 (46.5 mg, 0.2 mmol) and biboronic acid pinacol ester (B ₂ (pin) ₂ ) (60.9 mg, 2.4 mmol) were successively added successively respectively. );

C. the whole reaction system was stirred and reacted at room temperature, and the reaction time was 12 hours;

D. After the reaction is completed, the entire reaction system is filtered, and after the reaction is completed, the entire reaction system is filtered and washed with 2 mL of tetrahydrofuran. To the residue was directly added 244 mg of sodium perborate tetrahydrate, and the whole system was stirred at room temperature for 4 hours.

E. After the reaction, the entire reaction system was filtered, washed with 10 mL of ethyl acetate, and extracted with ethyl acetate (3×10 mL). After separating the organic phase, it was dried with anhydrous Na ₂ SO ₄ , filtered, and removed by rotary evaporation. solvent. The residue was purified by column chromatography with ethyl acetate/petroleum ether mixed solvent=4:1 to obtain III-13 pale yellow oily liquid, 34.5 mg, yield 69%.

The H NMR and C spectra of the target product are shown below:

¹ H NMR (400MHz); δ=8.01-7.98(m,2H), 7.28-7.26(m,1H), 7.17(t, J=8.6Hz,2H), 7.04-6.98(m,2H), 5.61- 5.58(m, 1H), 3.75(s, 1H), 3.54-3.41(m, 2H).

¹³ C NMR (100 MHz); δ=197.8, 167.3, 164.8, 146.6, 132.90, 132.87, 130.9, 130.8, 126.7, 124.7, 123.5, 115.9, 115.7, 77.3, 77.0, 76.7, 66.3, 47.1.

Example 17:

A preparation method of β-hydroxy compound III-14, the steps are:

A. Add 0.002 mmol of Y-type molecular sieve (Y-zeolite@CuSO ₄ ) loaded with copper ions into a 2.5 mL reaction tube, and add 1.0 mL of tetrahydrofuran and 1.0 mL of water, and stir at room temperature (20-25° C., the same below) for 1 Hour;

B. In the above system, α, β-unsaturated carbonyl compound I-14 (55.3 mg, 0.2 mmol) and biboronic acid pinacol ester (B ₂ (pin) ₂ ) (60.9 mg, 2.4 mmol) were successively added successively. );

C. the whole reaction system was stirred and reacted at room temperature, and the reaction time was 12 hours;

D. After the reaction is completed, the entire reaction system is filtered, and after the reaction is completed, the entire reaction system is filtered and washed with 2 mL of tetrahydrofuran. To the residue was directly added 244 mg of sodium perborate tetrahydrate, and the whole system was stirred at room temperature for 4 hours.

E. After the reaction, the entire reaction system was filtered, washed with 10 mL of ethyl acetate, and then extracted with ethyl acetate (3×10 mL). After separating the organic phase, it was dried with anhydrous Na ₂ SO ₄ , filtered, and removed by rotary evaporation. solvent. The residue was purified by column chromatography with ethyl acetate/petroleum ether mixed solvent=4:1 to obtain III-14 as a colorless oily liquid, 32.9 mg, yield 56%.

The H NMR and C spectra of the target product are shown below:

¹ H NMR (400MHz); δ=7.96 (d, J=7.0Hz, 2H), 7.65-7.55 (m, 5H), 7.50 (t, J=7.8Hz, 2H), 7.49 (t, J=7.7Hz) ,2H),5.43(dd,J=8.1,5.4Hz,1H),3.79(s,1H),3.41-3.31(m,2H).

¹³ C NMR (100 MHz); δ=199.8, 146.9, 136.3, 133.9, 130.3, 130.0, 129.6, 129.3, 128.8, 128.1, 126.0, 125.53, 125.50, 125.46, 125.42, 122.7, 77.3, 7.7.0, 7

Example 18:

A preparation method of β-hydroxy compound III-15, the steps are:

A. Add 0.002 mmol of Y-type molecular sieve (Y-zeolite@CuSO ₄ ) loaded with copper ions into a 2.5 mL reaction tube, and add 1.0 mL of tetrahydrofuran and 1.0 mL of water, and stir at room temperature (20-25° C., the same below) for 1 Hour;

B. In the above system, α, β-unsaturated carbonyl compound I-15 (53.7 mg, 0.2 mmol) and biboronic acid pinacol ester (B ₂ (pin) ₂ ) (60.9 mg, 2.4 mmol) were successively added successively respectively. );

C. the whole reaction system was stirred and reacted at room temperature, and the reaction time was 12 hours;

D. After the reaction is completed, the entire reaction system is filtered, and after the reaction is completed, the entire reaction system is filtered and washed with 2 mL of tetrahydrofuran. To the residue was directly added 244 mg of sodium perborate tetrahydrate, and the whole system was stirred at room temperature for 4 hours.

E. After the reaction, the entire reaction system was filtered, washed with 10 mL of ethyl acetate, and extracted with ethyl acetate (3×10 mL). After separating the organic phase, it was dried with anhydrous Na ₂ SO ₄ , filtered, and removed by rotary evaporation. solvent. The residue was purified by column chromatography with ethyl acetate/petroleum ether mixed solvent=4:1 to obtain III-15 as a white solid, 57.3 mg, yield>99%.

The H NMR and C spectra of the target product are shown below:

¹ H NMR (400 MHz); δ=7.95 (d, J=8.8 Hz, 2H), 7.37 (d, J=8.6 Hz, 2H), 6.94 (t, J=8.2 Hz, 4H), 5.29-5.26 (m ,1H),3.87(s,3H),3.81(s,3H),3.72(s,1H),3.34-3.25(m,2H).

¹³ C NMR (100 MHz); δ=198.9, 163.9, 159.0, 135.2, 130.5, 129.6, 127.0, 113.9, 113.8, 77.3, 77.0, 76.7, 69.8, 55.5, 55.3, 46.8.

Example 19:

A preparation method of β-hydroxy compound III-16, the steps are:

A. Add 0.002 mmol of Y-type molecular sieve (Y-zeolite@CuSO ₄ ) loaded with copper ions into a 2.5 mL reaction tube, and add 1.0 mL of tetrahydrofuran and 1.0 mL of water, and stir at room temperature (20-25° C., the same below) for 1 Hour;

B. In the above system, α, β-unsaturated carbonyl compound I-16 (48.1 mg, 0.2 mmol) and biboronic acid pinacol ester (B ₂ (pin) ₂ ) (60.9 mg, 2.4 mmol) were successively added successively. );

C. the whole reaction system was stirred and reacted at room temperature, and the reaction time was 12 hours;

D. After the reaction is completed, the entire reaction system is filtered, and after the reaction is completed, the entire reaction system is filtered and washed with 2 mL of tetrahydrofuran. To the residue was directly added 244 mg of sodium perborate tetrahydrate, and the whole system was stirred at room temperature for 4 hours.

E. After the reaction, the entire reaction system was filtered, washed with 10 mL of ethyl acetate, and then extracted with ethyl acetate (3×10 mL). After separating the organic phase, it was dried with anhydrous Na ₂ SO ₄ , filtered, and removed by rotary evaporation. solvent. The residue was purified by column chromatography with ethyl acetate/petroleum ether mixed solvent=4:1 to obtain III-16 as a white solid, 43.9 mg, yield 85%.

The H NMR and C spectra of the target product are shown below:

¹ H NMR (400 MHz); δ=7.86 (d, J=8.3 Hz, 2H), 7.42-7.39 (m, 2H), 7.27 (d, J=8.0 Hz, 2H), 7.08 (t, J=8.7 Hz) ,2H),5.33-5.29(m,1H),3.77(s,1H), 3.32-3.25(m,1H),2.42(s,3H).

¹³ C NMR (100 MHz); δ=199.7, 163.4, 160.9, 144.7, 138.74, 138.71, 134.0, 129.4, 128.2, 127.44, 127.36, 115.4, 115.2, 77.3, 77.0, 76.7, 69.5, 47.1, 21.

Example 20:

A preparation method of β-hydroxy compound III-17, the steps are:

A. Add 0.002 mmol of Y-type molecular sieve (Y-zeolite@CuSO ₄ ) loaded with copper ions into a 2.5 mL reaction tube, and add 1.0 mL of tetrahydrofuran and 1.0 mL of water, and stir at room temperature (20-25° C., the same below) for 1 Hour;

B. In the above system, α, β-unsaturated carbonyl compound I-17 (63.4 mg, 0.2 mmol) and biboronic acid pinacol ester (B ₂ (pin) ₂ ) (60.9 mg, 2.4 mmol) were successively added successively. );

C. the whole reaction system was stirred and reacted at room temperature, and the reaction time was 12 hours;

D. After the reaction is completed, the entire reaction system is filtered, and after the reaction is completed, the entire reaction system is filtered and washed with 2 mL of tetrahydrofuran. To the residue was directly added 244 mg of sodium perborate tetrahydrate, and the whole system was stirred at room temperature for 4 hours.

E. After the reaction, the entire reaction system was filtered, washed with 10 mL of ethyl acetate, and then extracted with ethyl acetate (3×10 mL). After separating the organic phase, it was dried with anhydrous Na ₂ SO ₄ , filtered, and removed by rotary evaporation. solvent. The residue was purified by column chromatography with ethyl acetate/petroleum ether mixed solvent=4:1 to obtain III-17 as a white solid, 30.8 mg, yield 46%.

The H NMR and C spectra of the target product are shown below:

¹ H NMR (400 MHz); δ=7.92 (d, J=8.9 Hz, 2H), 7.50 (d, J=8.4 Hz, 2H), 7.32-7.30 (m, 2H), 6.94 (d, J=8.9 Hz) ,2H),5.29-5.26(m,1H),3.874(br,1H), 3.867(s,3H),3.32-3.25(m,2H).

¹³ C NMR (100 MHz); δ=198.5, 164.0, 142.0, 131.5, 130.5, 129.4, 127.5, 121.3, 113.9, 69.5, 55.5, 46.7.

Example 21:

A preparation method of β-hydroxy compound III-18, the steps are:

A. Add 0.002 mmol of Y-type molecular sieve (Y-zeolite@CuSO ₄ ) loaded with copper ions into a 2.5 mL reaction tube, and add 1.0 mL of tetrahydrofuran and 1.0 mL of water, and stir at room temperature (20-25° C., the same below) for 1 Hour;

B. In the above system, α,β-unsaturated carbonyl compound I-18 (61.0 mg, 0.2 mmol) and biboronic acid pinacol ester (B ₂ (pin) ₂ ) (60.9 mg, 2.4 mmol) were successively added successively. );

C. the whole reaction system was stirred and reacted at room temperature, and the reaction time was 12 hours;

D. After the reaction is completed, the entire reaction system is filtered, and after the reaction is completed, the entire reaction system is filtered and washed with 2 mL of tetrahydrofuran. To the residue was directly added 244 mg of sodium perborate tetrahydrate, and the whole system was stirred at room temperature for 4 hours.

E. After the reaction, the entire reaction system was filtered, washed with 10 mL of ethyl acetate, and extracted with ethyl acetate (3×10 mL). After separating the organic phase, it was dried with anhydrous Na ₂ SO ₄ , filtered, and removed by rotary evaporation. solvent. The residue was purified by column chromatography with ethyl acetate/petroleum ether mixed solvent=4:1 to obtain III-18 as a pale yellow solid, 37.5 mg, yield 58%.

The H NMR and C spectra of the target product are shown below:

¹ H NMR (400 MHz); δ=7.99 (dd, J=8.9 Hz, 5.4 Hz, 2H), 7.51 (d, J=8.4 Hz, 1H), 7.32 (d, J=8.4 Hz, 2H), 7.16 ( t, J=8.6Hz, 2H), 5.32-5.28(m, 1H), 3.59(s, 1H), 3.29(s, 1H).

¹³ C NMR (100 MHz); δ=198.2, 167.4, 164.8, 141.8, 132.83, 132.80, 131.7, 130.9, 130.8, 127.4, 1215, 116.0, 115.8, 77.3, 77.2, 77.0, 76.7, 69.4, 47.1.

Example 22:

A preparation method of β-hydroxy compound III-19, the steps are:

A. Add 0.002 mmol of Y-type molecular sieve (Y-zeolite@CuSO ₄ ) loaded with copper ions into a 2.5 mL reaction tube, and add 1.0 mL of tetrahydrofuran and 1.0 mL of water, and stir at room temperature (20-25° C., the same below) for 1 Hour;

B. In the above system, α, β-unsaturated carbonyl compound I-19 (61.0 mg, 0.2 mmol) and biboronic acid pinacol ester (B ₂ (pin) ₂ ) (60.9 mg, 2.4 mmol) were successively added successively. );

C. the whole reaction system was stirred and reacted at room temperature, and the reaction time was 12 hours;

D. After the reaction is completed, the entire reaction system is filtered, and after the reaction is completed, the entire reaction system is filtered and washed with 2 mL of tetrahydrofuran. To the residue was directly added 244 mg of sodium perborate tetrahydrate, and the whole system was stirred at room temperature for 4 hours.

E. After the reaction, the entire reaction system was filtered, washed with 10 mL of ethyl acetate, and extracted with ethyl acetate (3×10 mL). After separating the organic phase, it was dried with anhydrous Na ₂ SO ₄ , filtered, and removed by rotary evaporation. solvent. The residue was purified by column chromatography with ethyl acetate/petroleum ether mixed solvent=4:1 to obtain III-19 as a white solid, 41.3 mg, yield 86%.

The H NMR and C spectra of the target product are shown below:

¹ H NMR (400 MHz); δ=7.77-7.74 (m, 2H), 7.46-7.44 (m, 2H), 7.41-7.35 (m, 4H), 7.33-7.29 (m, 1H), 5.36 (dd, J = 7.0, 5.1Hz, 1H), 3.64(s, 1H), 3.37-3.36(m, 2H), 2.41(s, 3H).

¹³ C NMR (100 MHz); δ=200.4, 142.9, 138.5, 136.6, 134.4, 128.7, 128.6, 128.5, 127.6, 125.7, 125.4, 77.3, 77.0, 76.7, 70.0, 47.4, 21.3.

Example 23:

A preparation method of β-hydroxy compound III-20, the steps are:

A. Add copper ion-loaded Y-type molecular sieve (Y-zeolite@CuSO ₄ ) into a 2.5mL reaction tube

0.002 mmol, and 1.0 mL of tetrahydrofuran and 1.0 mL of water were added, and stirred for 1 hour at room temperature (20-25 ° C, the same below);

B. To the above system, α, β-unsaturated carbonyl compound I-20 (61.0 mg, 0.2 mmol) and biboronic acid pinacol ester (B ₂ (pin) ₂ ) (60.9 mg, 2.4 mmol) were successively added successively. );

C. the whole reaction system was stirred and reacted at room temperature, and the reaction time was 12 hours;

D. After the reaction is completed, the entire reaction system is filtered, and after the reaction is completed, the entire reaction system is filtered and washed with 2 mL of tetrahydrofuran. To the residue was directly added 244 mg of sodium perborate tetrahydrate, and the whole system was stirred at room temperature for 4 hours.

E. After the reaction, the entire reaction system was filtered, washed with 10 mL of ethyl acetate, and extracted with ethyl acetate (3×10 mL). After separating the organic phase, it was dried with anhydrous Na ₂ SO ₄ , filtered, and removed by rotary evaporation. solvent. The residue was purified by column chromatography with ethyl acetate/petroleum ether mixed solvent=4:1 to obtain III-20 as a white solid, 54.7 mg, yield 94%.

The H NMR and C spectra of the target product are shown below:

¹ H NMR (400 MHz); δ=7.95 (d, J=8.9 Hz, 2H), 7.7.-7.70 (m, 1H), 7.35-7.31 (m, 2H), 7.25-7.20 (m, 1H), 6.93 (d, J＝9.0Hz, 2H), 5.67-5.61(m, 1H), 4.07(br, 1H), 3.86(s, 3H), 3.54-3.49(m, 1H), 3.11-3.04(m, 1H) ).

¹³ C NMR (100 MHz); δ=198.8, 163.9, 140.4, 131.1, 130.5, 129.4, 129.2, 128.5, 127.23, 127.18, 113.8, 66.9, 55.5, 44.8.

Example 24:

A preparation method of β-hydroxy compound III-21, the steps are:

A. Add copper ion-loaded Y-type molecular sieve (Y-zeolite@CuSO ₄ ) into a 2.5mL reaction tube

0.002 mmol, and 1.0 mL of tetrahydrofuran and 1.0 mL of water were added, and stirred for 1 hour at room temperature (20-25 ° C, the same below);

B. In the above system, α,β-unsaturated carbonyl compound I-21 (61.0 mg, 0.2 mmol) and biboronic acid pinacol ester (B ₂ (pin) ₂ ) (60.9 mg, 2.4 mmol) were successively added successively respectively. );

C. the whole reaction system was stirred and reacted at room temperature, and the reaction time was 12 hours;

D. After the reaction is completed, the entire reaction system is filtered, and after the reaction is completed, the entire reaction system is filtered and washed with 2 mL of tetrahydrofuran. To the residue was directly added 244 mg of sodium perborate tetrahydrate, and the whole system was stirred at room temperature for 4 hours.

E. After the reaction, the entire reaction system was filtered, washed with 10 mL of ethyl acetate, and then extracted with ethyl acetate (3×10 mL). After separating the organic phase, it was dried with anhydrous Na ₂ SO ₄ , filtered, and removed by rotary evaporation. solvent. The residue was purified by column chromatography with ethyl acetate/petroleum ether mixed solvent=4:1 to obtain III-21 as a white solid, 45.3 mg, yield 82%.

The H NMR and C spectra of the target product are shown below:

¹ H NMR (400MHz); δ=8.07-8.05 (m, 1H), 8.00-7.90 (m, 3H), 7.83-7.81 (m, 2H), 7.59-7.43 (m, 6H), 6.18 (dd, J =9.0,2.6Hz,1H),3.83(br,1H), 3.58-3.49(m,2H).

¹³ C NMR (100 MHz); δ=200.2, 138.4, 136.4, 133.7, 133.6, 129.8, 129.0, 128.6, 128.1, 128.0, 126.2, 125.6, 125.5, 123.1, 122.7, 66.7, 46.7.

Example 25:

A preparation method of β-hydroxy compound III-22, the steps are:

A. Add 0.002 mmol of Y-type molecular sieve (Y-zeolite@CuSO ₄ ) loaded with copper ions into a 2.5 mL reaction tube, and add 1.0 mL of tetrahydrofuran and 1.0 mL of water, and stir at room temperature (20-25° C., the same below) for 1 Hour;

B. In the above system, α, β-unsaturated carbonyl compound I-22 (61.0 mg, 0.2 mmol) and biboronic acid pinacol ester (B ₂ (pin) ₂ ) (60.9 mg, 2.4 mmol) were successively added successively. );

C. the whole reaction system was stirred and reacted at room temperature, and the reaction time was 12 hours;

D. After the reaction is completed, the entire reaction system is filtered, and after the reaction is completed, the entire reaction system is filtered and washed with 2 mL of tetrahydrofuran. To the residue was directly added 244 mg of sodium perborate tetrahydrate, and the whole system was stirred at room temperature for 4 hours.

E. After the reaction, the entire reaction system was filtered, washed with 10 mL of ethyl acetate, and then extracted with ethyl acetate (3×10 mL). After separating the organic phase, it was dried with anhydrous Na ₂ SO ₄ , filtered, and removed by rotary evaporation. solvent. The residue was purified by column chromatography with ethyl acetate/petroleum ether mixed solvent=4:1 to obtain III-22 as a white solid, 31.9 mg, yield 82%.

The H NMR and C spectra of the target product are shown below:

¹ H NMR (400MHz); δ=7.29-7.26(m,2H), 6.89(d,J=8.7Hz,2H), 5.12-5.08(m,1H), 3.80(s,3H), 3.23(s, 1H), 2.89-2.76(m, 2H), 2.19(s, 3H).

¹³ C NMR (100 MHz); δ=209.2, 159.1, 134.8 126.9, 113.9, 77.3, 77.0, 76.7, 69.5, 55.3, 51.9, 30.8.

Example 26:

A preparation method of β-hydroxy compound III-23, the steps are:

A. Add 0.002 mmol of Y-type molecular sieve (Y-zeolite@CuSO ₄ ) loaded with copper ions into a 2.5 mL reaction tube, and add 1.0 mL of tetrahydrofuran and 1.0 mL of water, and stir at room temperature (20-25° C., the same below) for 1 Hour;

B. In the above system, α, β-unsaturated carbonyl compound I-23 (61.0 mg, 0.2 mmol) and biboronic acid pinacol ester (B ₂ (pin) ₂ ) (60.9 mg, 2.4 mmol) were successively added successively respectively. );

C. the whole reaction system was stirred and reacted at room temperature, and the reaction time was 12 hours;

D. After the reaction is completed, the entire reaction system is filtered, and after the reaction is completed, the entire reaction system is filtered and washed with 2 mL of tetrahydrofuran. To the residue was directly added 244 mg of sodium perborate tetrahydrate, and the whole system was stirred at room temperature for 4 hours.

E. After the reaction, the entire reaction system was filtered, washed with 10 mL of ethyl acetate, and then extracted with ethyl acetate (3×10 mL). After separating the organic phase, it was dried with anhydrous Na ₂ SO ₄ , filtered, and removed by rotary evaporation. solvent. The residue was purified by column chromatography with ethyl acetate/petroleum ether mixed solvent=4:1 to obtain III-23 as a white solid, 15.1 mg, yield 30%.

The H NMR and C spectra of the target product are shown below:

¹ H NMR (400MHz); δ=7.91-7.88 (m, 2H), 7.54-7.50 (m, 1H), 7.42-7.38 (m, 2H), 7.33-7.31 (m, 2H), 7.26-7.22 (m ,2H),7.18-7.15(m,1H),6.65-6.61(m,1H),6.27(dd,J＝15.9Hz,6.0Hz,1H),4.89-4.86(m,1H),3.38(s, 1H), 3.26-3.16(m, 2H).

¹³ C NMR (100 MHz); δ=200.3, 136.54, 136.51, 133.6, 130.4, 130.2, 128.7, 128.5, 128.1, 127.7, 126.5, 77.3, 77.0, 76.7, 68.6, 45.2.

It can be drawn from the above embodiments that the method for preparing organoboron compounds and β-hydroxy compounds provided by the present invention has the characteristics of fast reaction rate, high yield, mild reaction conditions and simple process.

The above are only preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention shall be included in the protection of the present invention. within the range.

Claims (8)

1. A method for preparing an organic boron compound by catalysis of a copper ion-loaded Y-type molecular sieve is characterized by comprising the following steps:

A. adding a copper ion-loaded Y-type molecular sieve, tetrahydrofuran and water into a reaction container, and fully stirring at room temperature to obtain a mixed solution, wherein the ratio of the amount of copper ion-loaded substances loaded by the copper ion-loaded Y-type molecular sieve to the amount of water is 0.002-0.003 mmol: 1mL, wherein the volume ratio of tetrahydrofuran to water is 0.5-1: 1;

B. adding an alpha, beta-unsaturated carbonyl compound I and pinacol diboron into the mixed solution obtained in the step A, wherein the ratio of the alpha, beta-unsaturated carbonyl compound I to the water in the mixed solution is 0.15-0.25 mmol: 1mL, the ratio of the amount of pinacol diboron to the amount of the alpha, beta-unsaturated carbonyl compound I is 1.0-2.0: 1;

C. stirring and reacting at room temperature for 10-16 h;

D. after the reaction is finished, separating and purifying to obtain an organic boron compound II;

the chemical reaction equation is as follows:

wherein R is¹Is a phenylketon group, a p-methylphenylketon group, a p-methoxyphenylketon group, a p-fluorophenylketon group, an acetyl group or a pivaloyl group; r²Is phenyl, p-methylphenylP-methoxyphenyl, p-fluorophenyl, p-chlorophenyl, p-bromophenyl, p-trifluoromethylphenyl, m-bromophenyl, m-chlorophenyl, 2-thienyl, 2-naphthyl or styryl.

2. The method for preparing the organoboron compound by catalyzing the copper ion-loaded Y-type molecular sieve as claimed in claim 1, wherein: in the step A, the loading amount of copper ions in the copper ion-loaded Y-type molecular sieve is 5-10 wt%.

3. The method for preparing the organoboron compound by catalyzing the copper ion-loaded Y-type molecular sieve as claimed in claim 1, wherein: in step B, the mass ratio of pinacol diboron to α, β -unsaturated carbonyl compound I is 1.2: 1.

4. a method for preparing organoboron compound catalyzed by the copper ion-loaded Y-type molecular sieve as claimed in any one of claims 1 to 3, characterized in that: the specific steps of separation and purification in the step D are as follows: and after the reaction is finished, filtering the reaction liquid, washing a filter cake by using ethyl acetate, combining the filtrate with a washing liquid, extracting the filtrate by using ethyl acetate, separating an organic phase, drying the organic phase by using anhydrous sodium sulfate, filtering, removing the solvent in the filtrate by rotary evaporation, and separating and purifying the residue by using a mixed solvent column chromatography of the ethyl acetate and petroleum ether to obtain the compound.

5. A method for preparing a beta-hydroxy compound by catalysis of a copper ion-loaded Y-type molecular sieve is characterized by comprising the following steps:

A. adding a copper ion-loaded Y-type molecular sieve, tetrahydrofuran and water into a reaction container, and fully stirring at room temperature to obtain a mixed solution, wherein the dosage ratio of copper ions loaded by the copper ion-loaded Y-type molecular sieve to water is 0.01-0.015 mmol: 1mL, wherein the volume ratio of tetrahydrofuran to water is 0.5-1: 1;

B. adding an alpha, beta-unsaturated carbonyl compound I and pinacol diboron into the mixed solution obtained in the step A, wherein the dosage ratio of the alpha, beta-unsaturated carbonyl compound I to water in the mixed solution is 0.15-0.25 mmol: 1mL, the ratio of the amount of pinacol diboron to the amount of the alpha, beta-unsaturated carbonyl compound I is 1.0-2.0: 1;

C. stirring and reacting at room temperature for 10-16 h to obtain reaction liquid containing the organic boron compound II;

D. after the reaction is finished, filtering the reaction liquid, washing a filter cake with tetrahydrofuran, combining a washing liquid with the filtrate, adding sodium perborate tetrahydrate into the combined filtrate, stirring and reacting for 4-8 h at room temperature, wherein the ratio of the sodium perborate tetrahydrate to the amount of the alpha, beta-unsaturated carbonyl compound I added in the step B is 2.0-4.0: 1, the volume ratio of tetrahydrofuran used for washing in the step D to water added in the step A is 1.5-2: 1;

E. after the reaction is finished, separating and purifying to obtain a beta-hydroxy compound III;

the chemical reaction equation is as follows:

wherein R is¹Is a phenylketon group, a p-methylphenylketon group, a p-methoxyphenylketon group, a p-fluorophenylketon group, an acetyl group or a pivaloyl group; r²Is phenyl, p-methylphenyl, p-methoxyphenyl, p-fluorophenyl, p-chlorophenyl, p-bromophenyl, p-trifluoromethylphenyl, m-bromophenyl, m-chlorophenyl, 2-thienyl, 2-naphthyl, styryl.

6. The method for preparing beta-hydroxy compound by catalysis of the copper ion-loaded Y-type molecular sieve according to claim 5, wherein the method comprises the following steps: in the step A, the loading amount of copper ions in the copper ion-loaded Y-type molecular sieve is 5-10 wt%.

7. The method for preparing the beta-hydroxy compound by catalyzing the copper ion loaded Y-type molecular sieve according to claim 5, is characterized in that: in step B, the mass ratio of pinacol diboron to α, β -unsaturated carbonyl compound I is 1.2: 1.

8. the method for preparing beta-hydroxy compound by catalysis of the copper ion-loaded Y-type molecular sieve according to any one of claims 5 to 7, wherein: the specific steps of separation and purification in the step E are as follows: and after the reaction is finished, filtering, washing a filter cake by using ethyl acetate, combining the filtrate with a washing solution, extracting the filtrate by using ethyl acetate, separating an organic phase, drying the organic phase by using anhydrous sodium sulfate, filtering, removing the solvent in the filtrate by rotary evaporation, and separating and purifying the residue by using a mixed solvent column chromatography of the ethyl acetate and petroleum ether to obtain the compound.