CN111333591A - A kind of preparation method of 3-hydrazine-5-morpholinyl methyl-2-oxazolidinone - Google Patents

Abstract

The invention provides a preparation method of 3-hydrazine-5-morpholinyl methyl-2-oxazolidinone, belonging to the technical field of chemical synthesis. The preparation method comprises: subjecting 1-Boc-protected hydrazine-3-morpholine-2-propanol to a ring-closure reaction with carbonates to obtain 3-Boc-protected hydrazine-5-morpholinomethyl-2-oxazole Alkanone, and finally hydrolyzed to obtain AMOZ. Wherein, the chemical structural formula of 1-Boc protected hydrazine-3-morpholine-2-propanol is

The chemical structural formula of 3-Boc hydrazine-5-morpholinomethyl-2-oxazolidinone is

The chemical structural formula of AMOZ is

The carbonates include at least one of diethyl carbonate, dimethyl carbonate, di-tert-butyl carbonate and dipropyl carbonate. The above-mentioned method has a simple synthesis route, adopts a one-pot method to synthesize AMOZ and uses a catalyst in the preparation process, which greatly reduces the loss of the synthesis process, and the synthesis yield and recovery rate are high, which is suitable for mass production.

Description

A kind of preparation method of 3-hydrazine-5-morpholinyl methyl-2-oxazolidinone

technical field

The invention relates to the technical field of chemical synthesis, in particular to a preparation method of 3-hydrazine-5-morpholinomethyl-2-oxazolidinone.

Background technique

3-hydrazine-5-morpholinomethyl-2-oxazolidinone (AMOZ) is a metabolite of a nitrofuran drug, Furaltadone. By interfering with the oxidoreductase in the bacteria, it destroys the normal metabolism of the bacteria and makes the entire metabolic system chaotic, thereby playing a role in sterilization. The antibacterial spectrum of furanotadone is broad, and it can play an antibacterial effect on most Gram-positive and negative bacteria.

Because furanotazone has very good antibacterial effect, it is mainly used clinically for the treatment of various intestinal infectious diseases such as pullorum, chicken colibacillosis, chicken coccidiosis, and for promoting the growth of pigs, poultry and aquatic products. of additives.

The current method for synthesizing AMOZ has low synthetic yield and poor recovery. Therefore, it is of great significance to develop a new method for synthesizing AMOZ.

SUMMARY OF THE INVENTION

The objects of the present invention include providing a preparation method of AMOZ, the method has a simple synthetic route, adopts a one-pot method to synthesize the nitrofuran metabolite AMOZ, and uses a catalyst in the preparation process, which greatly reduces the loss of the synthesis process, and the synthetic product High yield and recovery rate, suitable for mass production.

The present invention solves its technical problem by adopting the following technical solutions to realize:

The present invention provides a method for preparing AMOZ, which comprises the following steps: subjecting 1-Boc hydrazine-3-morpholine-2-propanol to a ring-closing reaction with carbonate substances to obtain 3-Boc hydrazine-5-morpholinyl Methyl-2-oxazolidinone, and finally hydrolyzed to obtain the final product AMOZ.

3-Boc肼-5-吗啉基甲基-2-恶唑烷酮的化学结构式为

AMOZ的化学结构式为：

碳酸酯类物质包括碳酸二乙酯、碳酸二甲酯、碳酸二叔丁酯以及碳酸二丙酯中的至少一种。Wherein, the chemical structural formula of 1-Boc hydrazine-3-morpholine-2-propanol is

The chemical structural formula of 3-Boc hydrazine-5-morpholinomethyl-2-oxazolidinone is

The chemical structural formula of AMOZ is:

The carbonates include at least one of diethyl carbonate, dimethyl carbonate, di-tert-butyl carbonate and dipropyl carbonate.

The synthetic route is simple, adopts one-pot synthesis, reduces a large number of intermediate purification steps, and is beneficial to improve the yield.

In some alternative embodiments, the ring closure reaction is carried out in the presence of a basic catalyst. The catalyst is used in the preparation process, which greatly reduces the loss of the synthesis process, and the synthesis yield and recovery rate are high.

In some optional embodiments, the ring-closing reaction is carried out at 30-100°C for 2-7h; preferably at 60°C for 4h.

In some preferred embodiments, the ring-closure reaction is carried out by adding a basic catalyst to the reaction system of 1-Boc hydrazine-3-morpholine-2-propanol and diethyl carbonate at a temperature of 30-100° C. 2-7h.

In some alternative embodiments, the basic catalyst includes at least one of _NaOH , KOH, _Na2CO3 , and sodium methoxide.

In some optional embodiments, the molar ratio of 1-Boc hydrazine-3-morpholine-2-propanol to diethyl carbonate is 1:0.8-3, preferably 1:1.5.

In some alternative embodiments, 1-Boc hydrazine-3-morpholine-2-propanol is reconstituted with a first solvent, preferably, the first solvent comprises tetrahydrofuran, prior to mixing with diethyl carbonate.

Further, the preparation method of 1-Boc hydrazine-3-morpholine-2-propanol comprises: performing a ring-opening reaction between 1-morpholine-2,3-epoxypropane and Boc-protected hydrazine, 1-morpholine- The chemical structural formula of 2,3-propylene oxide is

In some preferred embodiments, the ring-opening reaction is carried out in the presence of an alcohol reagent or a furanic compound.

In some optional embodiments, the alcohol reagent includes ethanol or methanol; the furanic compound includes tetrahydrofuran.

In some alternative embodiments, the molar ratio of 1-morpholine-2,3-epoxypropane to hydrazine is 1:1-10, preferably 1:5.

Further, the ring-opening reaction is carried out under the condition of 15-30°C for 2-6h; more preferably, under the condition of 25°C for 4h.

In some optional embodiments, after the end of the ring-opening reaction, it also includes removing the remaining Boc-protected hydrazine and solvent, more preferably, removing the Boc-protected hydrazine and solvent by using an organic solvent extractive distillation method.

1-卤代-3-吗啉-2-丙醇中的卤素X为溴或者氯。Further, the preparation method of 1-morpholine-2,3-epoxypropane comprises: reacting 1-halo-3-morpholine-2-propanol with a base, 1-halo-3-morpholine-2 - The chemical structural formula of propanol is

Halogen X in 1-halo-3-morpholine-2-propanol is bromine or chlorine.

In some alternative embodiments, the 1-halo-3-morpholine-2-propanol and base are carried out in the presence of a second solvent, preferably, the second solvent includes tetrahydrofuran.

In some alternative embodiments, the molar ratio of 1-halo-3-morpholine-2-propanol to base is 1:1-5, more preferably 1:3.

Further, the 1-halo-3-morpholine-2-propanol and the base are reacted at 15-60° C. for 1-5 hours, preferably at 40° C. for 4 hours.

In some alternative embodiments, the base includes at least one of _NaOH , KOH, _Na2CO3 , sodium ethoxide, and sodium tert-butoxide.

In some optional embodiments, after the reaction between 1-halo-3-morpholine-2-propanol and the base is completed, it also includes removing the remaining organic solvent, preferably, removing the organic solvent by distillation.

卤代为溴代或者氯代。Further, the preparation method of 1-halo-3-morpholine-2-propanol comprises: reacting 1,3-dihalo-2-propanol with a base, and then performing S _N2 reaction with morpholine, 1 , The chemical structural formula of 3-dihalo-2-propanol is

Halogen is bromo or chloro.

In some optional embodiments, 1,3-dihalo-2-propanol is mixed with a base in a first alcohol solution for heating reaction, and then a second alcohol solution in which morpholine is dissolved is added for S _N2 reaction .

In some alternative embodiments, 1,3-dihalo-2-propanol is dissolved in the first alcohol solution, followed by addition of a base for heating reaction.

In some alternative embodiments, the molar ratio of 1,3-dihalo-2-propanol to base is 1:2-5, preferably 1:3.5.

In some alternative embodiments, the first alcoholic solution includes methanol solution and the second alcoholic solution includes ethanol solution.

In some optional embodiments, the heating reaction is carried out at 15-60 °C for 1-6 h, preferably at 50 °C for 3 h.

Further, the molar ratio of 1,3-dichloro-2-propanol to morpholine is 1:1-5, preferably 1:3.

In some optional embodiments, the _Sn2 reaction is carried out at 15-60°C for 2-10 hours, preferably at 40°C for 3 hours.

In some optional embodiments, after the _SN2 reaction is completed, it further includes removing the remaining first alcoholic solution and the second alcoholic solution.

Further, the preparation method of 1,3-dihalo-2-propanol comprises: mixing glycerol with trifluoroacetic anhydride, tris(dimethylamino)phosphine (HMPT) and lithium halide compounds in tetrahydrofuran solvent reaction.

In some optional embodiments, the lithium halide compound includes at least one of lithium chloride or lithium bromide.

In some optional embodiments, the molar ratio of glycerol to lithium halide compound is 1:5-15, more preferably 1:10.

Further, glycerol was placed in an oil bath, THF (tetrahydrofuran) was added, followed by trifluoroacetic anhydride, tris(dimethylamino)phosphine and lithium halide.

In some optional embodiments, glycerol and trifluoroacetic anhydride, tris(dimethylamino)phosphine and lithium halide compounds are carried out at 50-100°C for 5-24h, preferably at 80°C Condition for 12h.

In some optional embodiments, after the completion of the reaction of glycerol with trifluoroacetic anhydride, tris(dimethylamino)phosphine and lithium halide compounds, it also includes removing the remaining solvent, more preferably, using vacuum distillation way to remove the solvent.

The beneficial effects of the preparation method of AMOZ provided by the application include:

The preparation method of AMOZ provided by the present application is simple to operate, adopts a one-pot method to synthesize the nitrofuran metabolite AMOZ, and uses a protective group in the preparation process, which greatly reduces the loss of the synthesis process, and the synthesis yield and recovery rate are high .

Description of drawings

In order to explain the technical solutions of the embodiments of the present invention more clearly, the following briefly introduces the accompanying drawings used in the embodiments. It should be understood that the following drawings only show some embodiments of the present invention, and therefore do not It should be regarded as a limitation of the scope, and for those of ordinary skill in the art, other related drawings can also be obtained according to these drawings without any creative effort.

Fig. 1 is the synthetic route of AMOZ that the embodiment 1 of this application provides.

Detailed ways

In order to make the objectives, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be described clearly and completely below. If the specific conditions are not indicated in the examples, it is carried out according to the conventional conditions or the conditions suggested by the manufacturer. The reagents or instruments used without the manufacturer's indication are conventional products that can be purchased from the market.

The preparation method of 3-hydrazine-5-morpholinomethyl-2-oxazolidinone (AMOZ) provided in the examples of the present application will be specifically described below.

The chemical formula of AMOZ provided in this application is:

3-Boc肼-5-吗啉基甲基-2-恶唑烷酮的化学结构式为

AMOZ的化学结构式为：

碳酸酯类物质包括碳酸二乙酯、碳酸二甲酯、碳酸二叔丁酯以及碳酸二丙酯中的至少一种。The preparation method of the substance mainly includes the following steps: subjecting 1-Boc hydrazine-3-morpholine-2-propanol to a ring closure reaction with carbonate substances to obtain 3-Boc hydrazine-5-morpholinylmethyl-2 -Oxazolidinone, finally hydrolyzed to give the final product AMOZ. Wherein, the chemical structural formula of 1-Boc hydrazine-3-morpholine-2-propanol is

The chemical structural formula of 3-Boc hydrazine-5-morpholinomethyl-2-oxazolidinone is

The chemical structural formula of AMOZ is:

The carbonates include at least one of diethyl carbonate, dimethyl carbonate, di-tert-butyl carbonate and dipropyl carbonate.

For reference, in the preparation process, the molar ratio of 1-Boc hydrazine-3-morpholine-2-propanol to diethyl carbonate may be 1:0.8-3, such as 1:0.8, 1:1, 1:1.5 , 1:2, 1:2.5 or 1:3, etc., or other ratios in the range of 1:0.8-3, preferably 1:1.5.

In some optional embodiments, before mixing with diethyl carbonate, 1-hydrazine hydrate-3-morpholine-2-propanol can be reconstituted with a first solvent, wherein, for example, the first solvent can include Tetrahydrofuran. In addition, the first solvent may also include methanol, chloroform, or ethanol or the like.

For reference, the above-mentioned ring-closing reaction is carried out in the presence of a basic catalyst. Wherein, the basic catalyst may include, but is not limited to, at least one of NaOH, KOH, Na ₂ CO ₃ and sodium methoxide, preferably sodium methoxide.

In some optional embodiments, the ring closure reaction is to add a basic catalyst to the reaction system of 1-Boc hydrazine-3-morpholine-2-propanol and diethyl carbonate.

In some preferred embodiments, the above-mentioned ring-closing reaction is carried out under the conditions of 30-100°C (such as 30°C, 40°C, 50°C, 60°C, 70°C, 80°C, 90°C or 100°C, etc.) for 2- 7h (eg 2h, 3h, 4h, 5h, 6h or 7h). In some more preferred embodiments, the above ring-closing reaction is carried out at 60°C for 4h.

In some specific embodiments, 1-Boc hydrazine-3-morpholine-2-propanol can be added to tetrahydrofuran to dissolve, and then diethyl carbonate is added to the reconstituted solution according to the proportion, and the temperature is raised to 60° C. , and then the sodium methoxide solution dissolved in methanol was added to the above reaction system, and the reaction was carried out for 4h.

For reference, the above synthesis process can be expressed as

Further, the preparation method of 1-Boc hydrazine-3-morpholine-2-propanol may include: ring-opening reaction of 1-morpholine-2,3-epoxypropane with Boc-protected hydrazine, 1-morpholine The chemical structural formula of -2,3-epoxypropane is

For reference, the above-mentioned ring-opening reaction is carried out in the presence of an alcohol reagent or a furan compound. Wherein, the alcohol reagent includes ethanol or methanol, and the furan compound includes tetrahydrofuran.

For reference, in the preparation process, the molar ratio of 1-morpholine-2,3-epoxypropane to hydrazine hydrate may be 1:1-10, such as 1:1, 1:2, 1:5, 1:1: 6, 1:8 or 1:10, etc., and other ratios in the range of 1:1-10, preferably 1:5.

In some optional embodiments, the ring-opening reaction can be carried out at 15-30°C (eg, 15°C, 20°C, 25°C, or 30°C, etc.) for 2-6h (eg, 2h, 3h, 4h, 5h). or 6h, etc.), preferably at 25°C for 4h.

In some optional embodiments, after the end of the ring-opening reaction, it also includes removing the remaining Boc-protected hydrazine and solvent, for example, the Boc-protected hydrazine and solvent can be removed by extractive distillation with an organic solvent.

In a specific embodiment, 1-morpholine-2,3-epoxypropane and Boc-protected hydrazine can be placed in an ice-water bath respectively according to the ratio, and then ethanol is added respectively, and after the temperature drops to 0 °C, The ice-water bath was removed, and the timer was started after the solution returned to room temperature (25°C). After 4 hours of reaction, 1-Boc hydrazine-3-morpholine-2-propanol was obtained, extracted with ethyl acetate, and the Boc protection was removed by distillation under reduced pressure. hydrazine and solvent.

For reference, the above synthesis process can be expressed as

其中卤素X可以为溴和氯中的任何一种。Further, the preparation method of 1-morpholine-2,3-epoxypropane may include: reacting 1-halogenated 3-morpholine-2-propanol with a base, 1-halogenated-3-morpholine-2 - The chemical structural formula of propanol is

Wherein the halogen X can be any one of bromine and chlorine.

For reference, the reaction between 1-halo-3-morpholine-2-propanol and a base is carried out in the presence of a second solvent. Preferably, the second solvent may include, for example, THF (tetrahydrofuran). In addition, the second solvent may also include methanol, chloroform, or ethanol or the like.

In some alternative embodiments, the molar ratio of 1-halo-3-morpholine-2-propanol to base can be 1:1-5, such as 1:1, 1:2, 1:3, 1:1 4 or 1:5, etc., and other ratios in the range of 1:1-5, preferably 1:3.

In some alternative embodiments, the 1-halo-3-morpholine-2-propanol and base are at 15-60°C (eg, 15°C, 20°C, 30°C, 40°C, 50°C, or 60°C) etc.) for 1-5h (such as 1h, 2h, 3h, 4h or 5h, etc.), preferably at 40°C for 4h.

In some optional embodiments, the above-mentioned base may include, but is not limited to, at least one of NaOH, KOH, Na ₂ CO ₃ , sodium ethoxide, and sodium tert-butoxide.

In some optional embodiments, after the reaction between 1-halo-3-morpholine-2-propanol and the base is completed, it also includes removing the remaining organic solvent, for example, the organic solvent can be removed by distillation.

In a specific embodiment, 1-halogenated 3-morpholine-2-propanol can be dissolved in tetrahydrofuran first, then sodium ethoxide is added, and the reaction is carried out at room temperature (25° C.) for 5 hours. After the reaction is completed, distillation under reduced pressure is performed.

其中卤素X可以为溴和氯中的任何一种。For reference, the above synthesis process can be expressed as

Wherein the halogen X can be any one of bromine and chlorine.

其中卤素x可以为溴和氯中的任何一种。Further, the preparation method of 1-halo-3-morpholine-2-propanol may include: reacting 1,3-dihalo-2-propanol with a base, and then performing S _N2 reaction with morpholine, The chemical structural formula of 1,3-dihalo-2-propanol is

Wherein the halogen x can be any one of bromine and chlorine.

In some optional embodiments, 1,3-dihalo-2-propanol can be mixed with a base in the first alcohol solution for heating reaction, and then the second alcohol solution in which morpholine is dissolved is added to carry out S _N2 reaction.

In some alternative embodiments, 1,3-dihalo-2-propanol is dissolved in the first alcohol solution, followed by addition of a base for heating reaction.

In some alternative embodiments, the molar ratio of 1,3-dihalo-2-propanol to base may be 1:2-5, such as 1:2, 1:3, 1:4 or 1:5 etc., other ratios in the range of 1:2-5 are also possible, preferably 1:3.5.

In some alternative embodiments, the first alcoholic solution may include methanol solution, and the second alcoholic solution may include ethanol solution.

In some optional embodiments, the heating reaction can be carried out under the conditions of 15-60°C (eg 15°C, 20°C, 30°C, 40°C, 50°C or 60°C, etc.) for 1-6h (eg 1h, 2h) , 3h, 4h, 5h or 6h, etc.), preferably at 50°C for 3h.

In some alternative embodiments, the molar ratio of 1,3-dihalo-2-propanol to morpholine may be 1:1-5, such as 1:1, 1:2, 1:3, 1:1 4 or 1:5, etc., and other ratios in the range of 1:1-5, preferably 1:3.

In some optional embodiments, the _SN2 reaction can be carried out at 15-60°C (eg, 15°C, 20°C, 30°C, 40°C, 50°C or 60°C, etc.) for 2-10h (eg 2h, 4h, 5h, 6h, 8h or 10h, etc.), preferably at 40°C for 3h.

In some optional embodiments, after the _SN2 reaction is completed, it further includes removing the remaining first alcoholic solution and the second alcoholic solution.

In a specific embodiment, 1,3-dihalo-2-propanol can be dissolved in methanol first, stirred for 8 minutes, added KOH and reacted at room temperature (25°C) for 5 hours, and then dissolved The ethanolic solution of chlorophyll was added to the above reaction system, and the reaction was carried out for 5 h and then distilled under reduced pressure.

For reference, the above synthesis process can be expressed as

Further, the preparation method of 1,3-dihalo-2-propanol may include: mixing glycerol with trifluoroacetic anhydride, tris(dimethylamino)phosphine (HMPT) and lithium halide compounds in tetrahydrofuran solvent next reaction.

In some optional embodiments, the lithium halide compound includes at least one of lithium chloride or lithium bromide.

In some optional embodiments, the molar ratio of glycerol to the lithium halide compound is 1:5-15, such as 1:5, 1:7, 1:9, 1:11, 1:13, etc. , preferably 1:10.

In some alternative embodiments, glycerol is placed in an oil bath, the THF is added, followed by the trifluoroacetic anhydride, tris(dimethylamino)phosphine (HMPT) and lithium halide compounds.

In some optional embodiments, glycerol and trifluoroacetic anhydride, tris(dimethylamino)phosphine and lithium halide compounds are carried out at 50-100° C. for 5-24 h. Preferably, glycerol and trifluoroacetic anhydride, tris(dimethylamino)phosphine and lithium halide compounds are carried out at 80° C. for 12 h.

In some optional embodiments, after the glycerol reaction is completed, it also includes removing the remaining solvent, more preferably, removing the solvent by means of reduced pressure distillation.

For reference, the above synthesis process can be expressed as

The features and performances of the present invention will be further described in detail below in conjunction with the embodiments.

Example 1

Step 1: Dissolve glycerol (5g) in tetrahydrofuran (30ml) in a round-bottomed flask, add 27.13g of trifluoroacetic anhydride, stir at room temperature for 15-30min, use a rotary evaporator to remove trifluoroacetic acid. Then add the same volume of tetrahydrofuran, HMPT and lithium bromide, put it into an oil bath and reflux for 3-4 hours, remove tetrahydrofuran by a rotary evaporator, add saturated brine, use ethyl acetate for extraction three times and then distill to obtain a reaction intermediate product 1 , 3-dibromo-2-propanol.

Step 2: Dissolve the reaction product 1,3-dibromo-2-propanol in 10 mL methanol, stir for 10 minutes, add KOH (2.02 equiv), react at room temperature for 5 h, mix morpholine (1.5 equiv) with 10 mL A solution of ethanol was added to the reaction system. After continuing the reaction for 5 hours, 1-bromo-3-morpholine-2-propanol was obtained after distillation under reduced pressure.

Step 3: Take the above-mentioned reactant intermediate 1-bromo-3-morpholine-2-propanol, dissolve it with 10 mL of tetrahydrofuran, add sodium ethoxide (1.1 equiv.) into the reaction flask, react at room temperature for 5 h, then distill under reduced pressure , the intermediate 1-morpholine 2,3-epoxypropane was obtained.

Step 4: The above reaction products 1-morpholine 2,3-epoxypropane and Boc hydrazine (3 equivalents) were placed in an ice-water bath, respectively, and 5 mL of ethanol was added respectively. After the temperature dropped to 0 °C, the intermediate was added to complete Then, the ice-water bath was removed, and the time was started after the solution returned to room temperature. After 4 hours of reaction, the intermediate 1-Boc hydrazine-3-morpholine-2-propanol was obtained, and the hydrazine hydrate and other solvents were distilled off under reduced pressure.

Step 5: The intermediate 1-Boc hydrazine-3-morpholine-2-propanol was added to 15 mL of tetrahydrofuran to redissolve, and 10 mL of dissolved diethyl carbonate (1.5 equivalents) was added dropwise to the solution. Then the temperature was raised to 70° C., sodium methoxide solution (0.1 equivalent) dissolved in 0.5 ml of methanol was added dropwise to the reaction system, and the reaction was carried out for 4 h.

Step 6: The intermediate 3-Boc hydrazine-5-morpholinomethyl-2-oxazolidinone was added to dilute hydrochloric acid (2M) and ethyl acetate, stirred at room temperature for 6 hours, and then distilled under reduced pressure to obtain the product AMOZ.

The above-mentioned synthetic route can refer to Figure 1.

After structural identification, the obtained compound was indeed the target product 3-amino-5-morpholinylmethyl-2-oxazolidinone (AMOZ).

The synthetic yield of the above method was determined to be 8.6%.

Taking the most commonly used non-one-pot preparation method of AMOZ as control group 1, the synthesis yield of AMOZ prepared by the existing preparation method was 3.1%.

Comparing Example 1 and the control group, it can be seen that the synthetic yield of AMOZ prepared by the preparation method provided by the present application is higher than that of the control group, indicating that the preparation method provided by the present application can effectively improve the synthetic yield of AMOZ.

To sum up, the preparation method of AMOZ provided by the present application is simple to operate, adopts a one-pot method to synthesize the nitrofuran metabolite AMOZ, and uses a protective group in the preparation process, which greatly reduces the loss of the synthesis process, and the synthetic yield is improved. and recovery rates are high.

The above descriptions are only preferred embodiments of the present invention, and are not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and changes. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims (10)

1. a preparation method of 3-hydrazine-5-morpholinyl methyl-2-oxazolidinone, is characterized in that, comprises the following steps: 1-Boc hydrazine-3-morpholine-2-propanol is subjected to ring closure reaction with carbonates to obtain 3-Boc hydrazine-5-morpholinomethyl-2-oxazolidinone, which is finally hydrolyzed to obtain the final product AMOZ; Wherein, the chemical structural formula of described 1-Boc hydrazine-3-morpholine-2-propanol is

The chemical structural formula of the 3-Boc hydrazine-5-morpholinyl methyl-2-oxazolidinone is

The chemical structural formula of the AMOZ is:

The carbonates include at least one of diethyl carbonate, dimethyl carbonate, di-tert-butyl carbonate and dipropyl carbonate. 2. preparation method according to claim 1 is characterized in that, ring-closing reaction is to carry out under the condition that basic catalyst exists; Preferably, the ring-closing reaction is carried out under the condition of 30-100°C for 2-7h; more preferably, under the condition of 60°C for 4h; More preferably, the ring-closing reaction is to add the basic catalyst to the reaction system of the 1-Boc hydrazine-3-morpholine-2-propanol and the diethyl carbonate at a temperature of 30-100° C. 2-7h in the middle; Preferably, the basic catalyst includes at least one of NaOH, KOH, Na ₂ CO ₃ and sodium methoxide. 3. preparation method according to claim 2 is characterized in that, the molar ratio of described 1-Boc hydrazine-3-morpholine-2-propanol and described diethyl carbonate is 1:0.8-3, more The best is 1:1.5; Preferably, before mixing with the diethyl carbonate, the 1-Boc hydrazine-3-morpholine-2-propanol is reconstituted with a first solvent, more preferably, the first solvent includes tetrahydrofuran . 4. according to the preparation method described in any one of claim 1 to 3, it is characterized in that, the preparation method of described 1-Boc hydrazine-3-morpholine-2-propanol comprises: 1-morpholine-2, 3-epoxy propane and Boc-protected hydrazine carry out a ring-opening reaction, and the chemical structural formula of the 1-morpholine-2,3-epoxy propane is

Preferably, the ring-opening reaction is carried out in the presence of an alcohol reagent or a furan compound; Preferably, the alcohol reagent includes ethanol or methanol; Preferably, the furan-based compound includes tetrahydrofuran; Preferably, the molar ratio of the 1-morpholine-2,3-epoxypropane to the hydrazine is 1:1-10, preferably 1:5; Preferably, the ring-opening reaction is carried out under the condition of 15-30°C for 2-6h; more preferably, under the condition of 25°C for 4h; Preferably, after the ring-opening reaction is completed, it also includes removing the remaining Boc-protected hydrazine and solvent, and more preferably, removing the Boc-protected hydrazine and the solvent by using an organic solvent extractive distillation method. 5. The preparation method according to claim 4, wherein the preparation method of the 1-morpholine-2,3-epoxypropane comprises: 1-halogenated-3-morpholine-2-propanol With alkali reaction, the chemical structural formula of described 1-halogenated-3-morpholine-2-propanol is

The halogen X in the 1-halo-3-morpholine-2-propanol is bromine or chlorine; Preferably, the 1-halo-3-morpholine-2-propanol and the base are carried out in the presence of a second solvent, more preferably, the second solvent includes tetrahydrofuran; Preferably, the molar ratio of the 1-halo-3-morpholine-2-propanol to the base is 1:1-5, more preferably 1:3. 6. The preparation method according to claim 5, wherein the 1-halo-3-morpholine-2-propanol and the base are reacted under the condition of 15-60° C. for 1-5h, More preferably, the reaction is carried out under the condition of 40℃ for 4h; Preferably, the base comprises at least one of NaOH, KOH, Na ₂ CO ₃ , sodium ethoxide or sodium tert-butoxide; Preferably, after the reaction between the 1-halo-3-morpholine-2-propanol and the base is completed, it also includes removing the remaining organic solvent, and more preferably, removing the organic solvent by distillation. 7. The preparation method according to claim 5, wherein the preparation method of the 1-halogenated-3-morpholine-2-propanol comprises: 1,3-dihalogenated-2-propanol Reaction with base, followed by S _N2 reaction with morpholine, the chemical structural formula of the 1,3-dihalo-2-propanol is

Described halogen is bromo or chloro; Preferably, the 1,3-dihalo-2-propanol is mixed with the base in the first alcohol solution for heating reaction, and then the second alcohol solution in which morpholine is dissolved is added to carry out S _N2 reaction; Preferably, the 1,3-dihalo-2-propanol is dissolved in the first alcohol solution, and then the base is added for heating reaction; Preferably, the molar ratio of the 1,3-dihalo-2-propanol to the base is 1:2-5, more preferably 1:3.5; Preferably, the first alcohol solution includes methanol solution, and the second alcohol solution includes ethanol solution; Preferably, the heating reaction is carried out at 15-60°C for 1-6h, more preferably at 50°C for 3h. 8. preparation method according to claim 7, is characterized in that, the mol ratio of described 1,3-dihalogenated-2-propanol and described morpholine is 1:1-5, is more preferably 1:1: 3; Preferably, the Sn2 reaction is carried out at 15-60°C for _2-10h , more preferably at 40°C for 3h; Preferably, after the _SN2 reaction is completed, the method further includes removing the remaining first alcoholic solution and the second alcoholic solution. 9. preparation method according to claim 7 is characterized in that, the preparation method of described 1,3-dihalo-2-propanol comprises: react glycerol with trifluoroacetic anhydride, tris(dimethylamino)phosphine and lithium halide compounds in tetrahydrofuran solvent; Preferably, the lithium halide compound includes at least one of lithium chloride or lithium bromide; Preferably, the molar ratio of the glycerol to the lithium halide compound is 1:5-15, more preferably 1:10; Preferably, the glycerol is placed in an oil bath, tetrahydrofuran is added, and then the trifluoroacetic anhydride, tris(dimethylamino)phosphine and lithium halide compounds are added. 10 . The preparation method according to claim 9 , wherein the glycerol and the trifluoroacetic anhydride, the tris(dimethylamino) phosphine and the lithium halide compound have a temperature of 50-100 ℃. 11 . 5-24h under the condition of ℃; Preferably, the glycerol, the trifluoroacetic anhydride, the tris(dimethylamino)phosphine and the lithium halide compound are carried out at 80° C. for 12 h; Preferably, after the completion of the reaction of the glycerol with the trifluoroacetic anhydride, the tris(dimethylamino)phosphine and the lithium halide compound, the method further includes removing the remaining solvent. The solvent was removed by means of pressure distillation.

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