CN102532079B - Preparation method of Corey Lactone 3-benzoate - Google Patents

Abstract

The invention provides a preparation method of benzoyl core lactone. Starting from Cory lactone, obtain Cory lactone dibenzoate through benzoylation reaction, and then creatively use the transesterification reaction under acidic conditions to selectively remove a benzoyl group to obtain the product. The method provided by the invention is simple to operate, does not need to use expensive protective groups, does not need chromatographic separation in the later stage, has mild reaction conditions, high product yield, good purity, low production cost, and has good industrialization prospects.

Description

The preparation method of benzoyl core lactone

technical field

The invention relates to a preparation method of benzoyl core lactone. the

Background technique

Benzoyl lactone stands for (-) benzoyl lactone or its enantiomer (+) benzoyl lactone or racemate (±) benzoyl lactone . The full name of (-) benzoyl core lactone is (3aR, 4S, 5R, 6aS)-(-)-5-benzoyloxy-hexahydro-4-hydroxymethyl-2H-cyclopenta [b]furan-2-one ((3aR,4S,5R,6aS)-4-hydroxymethyl-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl benzoate); molecular formula: C ₁₅ H ₁₆ O ₅ ; Molecular weight: 276.28; CAS No.: 39746-00-4; its structure is as follows:

The full name of (+) benzoyl core lactone is (3aS, 4R, 5S, 6aR)-(+)-5-benzoyloxy-hexahydro-4-hydroxymethyl-2H-cyclopenta[ b] furan-2-one ((3aS,4R,5S,6aR)-4-hydroxymethyl-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl benzoate); molecular formula: C ₁₅ H ₁₆ O ₅ ; molecular weight : 276.28; CAS: 53275-53-9; its structure is as follows:

Benzoylcolides are important intermediates of PG drugs, but there are few direct literature reports on their synthesis. The literature Nature Chemical Biology2009, 26-28 obtains benzoyl corylide from the demethylation of the methylated derivative; patents US6353000 and US6353014 obtain benzoyl corylide from the reduction of the corresponding aldehyde. The raw materials used in the above two methods are not easy to obtain, the cost is relatively high, and they are not suitable for industrialized production. the

Another method is to use Cory lactone as a raw material to selectively introduce a benzoyl group on a secondary hydroxyl group to synthesize the target product. Cory lactone is a common intermediate, and it is easy to obtain (Tetrahedron letters1976, 4639-4642), so the preparation of benzoyl cory lactone from cory lactone is a more practical route. At present, the more typical approach is to selectively protect the primary hydroxyl group with a large steric hindrance protecting group (such as tert-butyldimethylsilyl/triphenylmethyl group), then benzoylate the secondary hydroxyl group, and then remove the Large sterically hindered protecting groups give products (eg Tetrahedron Letters 2004, 1973-1976). However, this method also has limitations: the reagents used, such as tert-butyldimethylsilyl chloride and triphenylchloromethane, are relatively expensive, and the molecular weight is relatively large, which greatly increases the cost; the intermediate is not easy to separate and purify, and the impurities are brought down One step; the final product is also difficult to crystallize and purify. Generally, it needs to be separated and purified by column chromatography, which prolongs the production cycle and increases the cost. the

Invention content:

Based on the above status quo, the present invention utilizes the transesterification reaction under acidic conditions to selectively remove a benzoyl group from coli lactone dibenzoate lipid coli lactone dibenzoate (structure shown in the figure below), Benzoyl coli lactone is obtained. Among them, coli lactone dibenzoate can be easily obtained from coli lactone through benzoylation, and the reaction effect is good, and the product is easy to crystallize and purify. the

The preparation method of benzoyl coli lactone provided by the invention comprises the following steps (see Fig. 1):

(A) Benzoylation reaction: Cory lactone undergoes a benzoylation reaction to obtain Cory lactone dibenzoate Cory lactone dibenzoate;

The core lactones include (-) core lactone and its derivatives, (+) core lactone and its derivatives, and (±) core lactone and its derivatives. the

(B) transesterification reaction: coli lactone dibenzoate coli lactone dibenzoate removes a benzoyl group through transesterification to obtain benzoyl coli lactone;

The core lactone dibenzoate core lactone dibenzoate comprises (-) core lactone dibenzoate, (+) core lactone dibenzoate and (±) Cory lactone dibenzoate;

The benzoyl coli lactones include (-) benzoyl coli lactone, (+) benzoyl coli lactone and (±) benzoyl coli lactone. the

The preferred technical scheme of the preparation method of benzoyl coli lactone provided by the invention is:

(A) Benzoylation reaction: coli lactone reacts with benzoyl chloride to obtain coli lactone dibenzoate;

(B) Transesterification reaction: Under acidic conditions, corylide dibenzoate undergoes a transesterification reaction to remove a benzoyl group to obtain benzoyl corylide. the

The more preferred technical scheme of the preparation method of benzoyl coli lactone provided by the invention is:

(A) Benzoylation reaction: at -20°C-100°C, Cory lactone and benzoyl chloride react to obtain the product Cory lactone dibenzoate;

(B) transesterification reaction:

(a) Dissolve coli lactone dibenzoate in solvent _S2 , react under acidic conditions at a temperature of 0-200°C for 1-100 hours, distill off solvent _S2 , and obtain coli lactone and benzene Formylcolide mixture;

(b) dissolving the mixture of coli lactone and benzoyl coli lactone in the organic solvent _S3 , and washing with water;

(c) Evaporating the water layer to dryness to recover coli lactone; evaporating the organic layer to dryness, crystallizing with solvent _S4 , and suction filtering to obtain benzoyl coli lactone.

A more preferred solution for the step (A) benzoylation reaction is: mix coli lactone with solvent S ₁ , add base B ₁ and catalyst C ₁ , add benzoyl chloride dropwise at 0-40°C, After the drop is completed, react at 0-40°C for 5-20 hours; after post-treatment, the product Cory lactone dibenzoate is obtained.

Wherein, the mass/volume ratio of coli lactone to solvent S ₁ is preferably 1:1-100; most preferably 1:3-10.

The molar ratio of Cory lactone to base B ₁ , catalyst C ₁ and benzoyl chloride is preferably 1:2-4:0-1:2-4; most preferably 1:1-1.5:0-1:2- 3.

The solvent S ₁ is preferably dichloromethane, chloroform, ethyl acetate, tetrahydrofuran, 1,2-dichloroethane, acetonitrile, DMF and/or toluene; most preferably dichloromethane and/or chloroform.

The base B is _preferably triethylamine, diisopropylethylamine, DBU, pyridine, sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, potassium carbonate and/or cesium carbonate; most preferably triethylamine amine and/or diisopropylethylamine.

The catalyst C ₁ is preferably DMAP, DBU, 2,6-lutidine and/or 3,5-lutidine; it is preferably DMAP.

The post-treatment method is pickling, alkali washing, and then distilling off the solvent. the

In step (B) transesterification reaction:

A more preferred solution of the step (a) is: dissolving coli lactone dibenzoate in solvent S ₂ , and reacting for 10-20 hours at a temperature of 50-100° C. under acidic conditions. The molar concentration of coli lactone dibenzoate in solvent _S2 is preferably 0.1-3mol/L; most preferably 0.3-1mol/L.

The _S2 is preferably: tert-butanol, isopropanol, neopentyl alcohol, pentaerythritol, isobutanol, n-butanol, n-propanol, ethanol, methanol, ethylene glycol, glycerol, PEG, benzyl alcohol, phenethyl alcohol , phenylpropanol, phenol, diphenyl alcohol, diacetone alcohol, hexanol, heptanol, octanol, nonanol, decanol and/or cetyl alcohol; most preferably tert-butanol and/or isopropanol.

Described under acidic condition is adding sulfuric acid, selenic acid, methanesulfonic acid, p-toluenesulfonic acid, trifluoromethanesulfonic acid, sulfur trioxide, sulfurous acid, sulfur dioxide, carbon dioxide, nitrogen dioxide, cation exchange resin, formic acid, Benzoic acid, acetic acid, phenylacetic acid, oxalic acid, propionic acid, acrylic acid, malonic acid, butyric acid, succinic acid, citric acid, tartaric acid, lactic acid, pyruvic acid, gluconic acid, malic acid, valeric acid, glutaric acid , palmitic acid, stearic acid, palmitic acid, oleic acid, trichloroacetic acid, trifluoroacetic acid, hydrocyanic acid, hydrofluoric acid, hydrochloric acid, nitric acid, nitrous acid, phosphoric acid, hydrogen bromide, hydrogen iodide, chlorine acid, perchloric acid, bromic acid, iodic acid, periodic acid, phosphorus pentoxide, p-nitrophenol, boric acid, fluoroboric acid, fluorophosphoric acid, boron trifluoride, aluminum chloride, zinc chloride, or bromide zinc; most preferably adding sulfuric acid, methanesulfonic acid. The added amount is preferably: the molar concentration in the solvent _S2 is 0.01-10 mol/L; most preferably 0.05-2 mol/L.

In step (b), the organic solvent S is _preferably ethyl acetate, dichloromethane, chloroform, 1,2-dichloroethane, methyl tert-butyl ether and/or diethyl ether; most preferably ethyl acetate and/or or dichloromethane.

In step (c), the solvent S ₄ is preferably carbon tetrachloride, toluene, petroleum ether, hexane and/or ethyl acetate; most preferably carbon tetrachloride and/or toluene.

The solvent S ₂ in the step (a), the organic solvent S ₃ in the step (b) and the solvent S ₄ in the step (c), the volume ratios of the three are: S ₃ :S ₂ =1: 1-10; S ₄ :S ₂ =1:1-10; most preferably S ₃ :S ₂ =1:1-5; S ₄ :S ₂ =1:1-5.

The invention selectively removes a benzoyl group in a bisbenzoyl compound by means of acidic transesterification for the first time, and is applied to the synthesis of benzoyl core lactone. The remarkable advantage of this method is that more expensive protective reagents such as tert-butyldimethylsilyl chloride and triphenylchloromethane are completely omitted, and are completely replaced by cheap benzoyl chloride. Due to the use of a single benzoyl cyclic protection and deprotection, all intermediates can be recycled repeatedly, reducing the complexity of the reaction, making the synthesis process simple, post-processing convenient, high material utilization rate, easy purification of products, and easy industrialization. the

Description of drawings: Figure 1 is a schematic flow chart of the preparation method

Detailed ways:

The present invention is further specifically described below in conjunction with the examples, but the present invention is not limited to these examples. the

The following examples select (-) coli lactone and its derivatives, but the method used is also applicable to (+) coli lactone derivatives and (±) coli lactone derivatives (see Figure 1). The remarkable advantage of this method is that more expensive protecting groups such as tert-butyldimethylsilyl chloride and triphenylchloromethane are completely omitted, and are completely replaced by cheap benzoyl chloride. Due to the use of a single benzoyl group for protection and deprotection, all intermediates can be recycled repeatedly, which reduces the complexity of the reaction and significantly improves the utilization rate of materials. The total yield of the target product is about 95%, and the purity is 99.7%, ee The value is 99.8%, which is far better than other methods (such as using tert-butyldimethylchlorosilane as a protective agent, the total yield of the product is about 50%; the purity of the product obtained at one time is about 95%, which needs to be further refined). the

Embodiment 1: (-) Cory lactone dibenzoate preparation:

Add 100g (1eq) (-) coli lactone into a 2000ml three-necked flask, add 500ml dichloromethane and stir to suspend it, then add 202ml (2.5eq) triethylamine and 3.5g (0.05eq) DMAP at room temperature, while stirring 148.5ml (2.2eq) of benzoyl chloride was added dropwise, and stirred at room temperature for 20h. At this time, TLC monitoring showed that there was no raw material. The reaction solution was washed with 750ml of 1mol/L hydrochloric acid, the organic phase was separated, and 500ml of saturated aqueous sodium bicarbonate solution was added to stir for 0.5h, the organic phase was separated, dried over anhydrous sodium sulfate, filtered, and the filtrate was evaporated to dryness to obtain 230g (-) coli lactone Dibenzoate, off-white solid, crude yield 100%. the

Embodiment 2: (-) preparation of benzoyl core lactone:

Add 50g (-) coli lactone dibenzoate to a 1000ml one-mouth bottle, add 500ml isopropanol and 20ml 1M sulfuric acid, and heat to reflux for 24h while stirring. Cool, evaporate the solvent to dryness, dissolve in 300ml of dichloromethane and 300ml of water, separate the organic phase, and wash with 200ml of water. The organic phase was dried with anhydrous sodium sulfate, filtered, the filtrate was evaporated to dryness, 100ml of toluene was added to stir and crystallize, and 11.6g (-) benzoyl corylide was obtained by suction filtration, with a yield of 32%, a purity of 99.7%, and an ee value of 99.8 %. The water phase was evaporated to dryness, dissolved in 100ml ethyl acetate and 20ml methanol, filtered through a silica gel pad, washed with 100ml ethyl acetate, and the filtrate was evaporated to dryness to obtain 13g (-) coli lactone, with a recovery rate of 57%, which can be recycled. The toluene mother liquor was evaporated to dryness, then evaporated to dryness under high vacuum and reduced pressure, and the obtained residue was dissolved in isopropanol and directly returned to the transesterification reaction system for recycling. After many times of material recovery and recycling, the total yield of this step reaction is about 95%. the

Embodiment 3: (-) Cory lactone dibenzoate preparation:

Add 1 kg (-) Cory lactone in the 20L reactor, add 6 kg of dichloromethane and stir to make it suspended, add 2L triethylamine and 35g DMAP successively at room temperature, add 1.75 kg of benzoyl chloride dropwise under stirring, and the reaction is released. As the temperature rises, the addition rate is controlled to keep the reaction mixture under reflux slowly, and the drop is completed in about 3 hours. At this time, TLC detection shows that there is no raw material. The reaction solution was washed with 8L 1mol/L hydrochloric acid, the organic phase was separated, dried over anhydrous sodium sulfate, filtered, the filtrate was evaporated until a small amount of solvent remained, added 3L methanol, stirred and crystallized, filtered with suction, and dried to obtain 2.1 kg (-) coli lactone Dibenzoate, off-white powder, yield 92%, purity 98.5%. the

Embodiment 4: (-) preparation of benzoyl core lactone:

Add 1 kg of (-) Cory lactone dibenzoate to a 20L reactor, add 5 kg of tert-butanol, 3 kg of methanesulfonic acid and 1 kg of water, and heat to reflux for 10 h while stirring. Cool, evaporate the solvent to dryness, dissolve in 6L ethyl acetate and 6L water, separate the organic phase, and wash with 3L water. The organic phase was dried with anhydrous sodium sulfate, filtered, and the filtrate was evaporated to dryness, added 2L carbon tetrachloride and stirred and crystallized, and suction filtered to obtain 0.31 kg of (-) benzoyl coli lactone, with a yield of 43%, a purity of 95%, The ee value is 99%. The water phase was evaporated to dryness, dissolved in 2L ethyl acetate and 0.4L methanol, filtered through silica gel, rinsed with 2L ethyl acetate, and the filtrate was evaporated to dryness to obtain 153g (-) coli lactone, with a recovery rate of 40%, which can be recycled. The carbon tetrachloride mother liquor was evaporated to dryness, then evaporated to dryness under high vacuum and reduced pressure, and the obtained residue was dissolved in tert-butanol and directly returned to the transesterification reaction system for recycling. After several times of material recovery and recycling, the total yield of this step reaction is about 90%. the

Embodiment 5: (+) Cory lactone dibenzoate preparation:

Add 100g (1eq) (+) Cory lactone into a 2000ml three-necked flask, add 450ml of dichloromethane and stir to suspend it, add 195ml of triethylamine and 2g of DMAP in sequence at 20°C, and add 150ml of benzoyl chloride dropwise while stirring After about 1.5 hours, the mixture was stirred at 40° C. for 4 hours. At this time, TLC monitoring showed that there was no raw material. The reaction solution was washed with 700ml of 1mol/L hydrochloric acid, the organic phase was separated, and 500ml of saturated aqueous sodium bicarbonate solution was added to stir for 0.5h. The organic phase was separated, dried over anhydrous sodium sulfate, filtered, and the filtrate was evaporated until a small amount of solvent remained. crystallized, cooled to 0°C, suction filtered, transferred and rinsed with a small amount of cold methanol, and dried to obtain 215g (+) Cory lactone dibenzoate, an off-white powder with a yield of 94% and a purity of 96%. . the

Embodiment 6: (+) preparation of benzoyl core lactone:

Add 84.8g (+) coli lactone dibenzoate to a 2000ml single-necked bottle, add 800ml isobutanol, 50g p-toluenesulfonic acid and 50ml water, and heat to reflux for 16h while stirring. Cool, evaporate the solvent to dryness, dissolve in 500ml of dichloromethane and 300ml of water, separate the organic phase, and wash with 300ml of water. The organic phase was dried with anhydrous sodium sulfate, filtered, and the filtrate was evaporated to dryness, 200ml of toluene was added to stir and crystallize, and 23g (+) benzoyl corylide was obtained by suction filtration, with a single cycle yield of 37% and a purity of 95%. The aqueous phase was evaporated to dryness, dissolved in 160ml ethyl acetate and 30ml methyl alcohol, filtered through a silica gel pad, washed with 160ml ethyl acetate, and the filtrate was evaporated to dryness to obtain 15.58g (+) coli lactone, which was reclaimed by the method of example 5 ( +) coli lactone is made into (+) coli lactone dibenzoate, merges with toluene mother liquor, evaporates to dryness, and the method for the residue obtained therefrom obtains 10.68g (+) benzoylacetate again with the method above example 6 Lilactone, the 10.86g (+) Cory lactone that reclaims and the toluene mother liquor combine and use the method for example 5 to make (+) Cory lactone dibenzoate by the (+) Cory lactone that this reclaims , Obtain 31.3g (+) core lactone dibenzoate, yield 87%. Therefore, through two times of material recovery and recycling, the reaction actually consumes 53.5g (+) coli lactone dibenzoate, and a total of 33.86g (+) benzoyl coli lactone is obtained, with a yield of 87%. the

Embodiment 7: (±) preparation of benzoyl core lactone:

Add 100g (±) Cory lactone into a 2000ml three-necked flask, add 500ml dichloromethane and stir to suspend, add 190ml triethylamine and 2.5g DMAP in turn at room temperature, add 150ml benzoyl chloride dropwise while stirring, and stir at room temperature for 20h . The reaction solution was washed with 700ml1mol/L hydrochloric acid, the organic phase was separated, dried over anhydrous sodium sulfate, filtered, and the filtrate was evaporated to dryness to give 228g (±) coli lactone dibenzoate, off-white solid. The obtained crude solid was directly added with 1000ml of isopropanol and 40ml of 1M sulfuric acid, and heated under reflux for 30h while stirring. Cool, evaporate the solvent to dryness, dissolve in 600ml of dichloromethane and 600ml of water, separate the organic phase, and wash with 400ml of water. The organic phase was dried with anhydrous sodium sulfate, filtered, and the filtrate was evaporated to dryness, 150ml of toluene was added to stir and crystallize, and 25g (±) benzoyl corylide was obtained by suction filtration with a purity of 99%. The water phase was evaporated to dryness, dissolved in 200ml ethyl acetate and 40ml methanol, filtered through a silica gel pad, washed with 200ml ethyl acetate, and the filtrate was evaporated to dryness to obtain 30g (±) coli lactone, which can be recycled. The toluene mother liquor was evaporated to dryness, and the resulting residue was dissolved in isopropanol to repeat the transesterification operation for recycling. the

The above embodiments are for the purpose of illustration only, 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 should be included within the protection scope of the present invention . the

Claims (19)

1. a preparation method of benzoyl coli lactone, is characterized in that comprising the steps: (A) Benzoylation reaction: at -20°C-100°C, Cory lactone and benzoyl chloride react to obtain the product Cory lactone dibenzoate; (B) transesterification reaction: (a) Dissolve coli lactone dibenzoate in solvent _S2 , react under acidic conditions at a temperature of 0-200°C for 1-100 hours, distill off solvent _S2 , and obtain coli lactone and benzene Formylcolide mixture; (b) dissolving the mixture of coli lactone and benzoyl coli lactone in the organic solvent _S3 , and washing with water; (c) Evaporating the aqueous layer to dryness to recover coli lactone; evaporating the organic layer to dryness, crystallizing with solvent _S4 , and suction filtering to obtain benzoyl coli lactone; In step (a), the solvent _S2 is selected from: tert-butanol, isopropanol and/or isobutanol; In step (b), the organic solvent _S3 is selected from ethyl acetate, dichloromethane, chloroform, 1,2-dichloroethane, methyl tert-butyl ether and/or diethyl ether; In step (c), the solvent S ₄ is selected from carbon tetrachloride, toluene, petroleum ether, hexane and/or ethyl acetate. 2. The preparation method according to claim 1, characterized in that in the step (a), the solvent _S2 is selected from: tert-butanol and/or isopropanol. 3. The preparation method according to claim 1, characterized in that in the step (a), the molar concentration of coli lactone dibenzoate in the solvent _S2 is 0.1-3mol/L. 4. The preparation method according to claim 1, characterized in that in the step (a), the acidic condition is achieved by adding sulfuric acid, methanesulfonic acid and/or p-toluenesulfonic acid. 5. The preparation method according to claim 4, characterized in that in the step (a), the acidic condition is achieved by adding sulfuric acid and methanesulfonic acid. 6. The preparation method according to claim 1, characterized in that in the step (a), the acidic condition is achieved by adding sulfuric acid, methanesulfonic acid and/or p-toluenesulfonic acid, and the amount added For: the molar concentration in solvent _S2 is 0.01-10mol/L. 7. The preparation method according to claim 1, characterized in that in the step (b), the organic solvent _S3 is selected from ethyl acetate and/or dichloromethane. 8. The preparation method according to claim 1, characterized in that in the step (c), the solvent _S4 is selected from carbon tetrachloride and/or toluene. 9. The preparation method according to claim 1, characterized in that: The step (a) is: dissolving coli lactone dibenzoate in solvent _S2 , and reacting for 10-20 hours at a temperature of 50-100°C under acidic conditions; solvent _S2 is selected from tert-butyl Alcohol and/or isopropanol; The molar concentration of Cory lactone dibenzoate in solvent S ₂ is 0.1-3mol/L; Described is to add sulfuric acid and methanesulfonic acid to realize under acidic conditions, and add The amount is: the molar concentration in the solvent _S2 is 0.01-10mol/L; In the step (b): solvent _S3 is selected from ethyl acetate and/or dichloromethane; In the step (c): the solvent _S4 is selected from carbon tetrachloride and/or toluene; Moreover, the amounts of the solvent S ₂ in the step (a), the organic solvent S ₃ in the step (b) and the solvent S ₄ in the step (c) are respectively in volume ratio: S ₃ :S ₂ =1:1-10; S ₄ :S ₂ =1:1-10. 10. The preparation method according to claim 9, characterized in that: The molar concentration of Cory lactone dibenzoate in solvent _S2 is 0.3-1mol/L, and the molar concentration of sulfuric acid and methanesulfonic acid in solvent _S2 is 0.05-2mol/L, _S3 : _S2 , S ₄ :S ₂ are all 1:1~5. 11. The preparation method according to any one of claims 1-10, characterized in that the step (A) benzoylation reaction comprises: Mix coli lactone with solvent S ₁ , add base B ₁ and catalyst C ₁ , add benzoyl chloride dropwise at -20°C-50°C, and react at -20°C-100°C for 1 to 20 hours after dropping ; Obtain product Cory lactone dibenzoate through aftertreatment; The solvent _S is selected from dichloromethane, chloroform and/or 1,2-dichloroethane; The base B _is selected from triethylamine, diisopropylethylamine, DBU and/or pyridine; The catalyst _C1 is selected from DMAP, DBU, 2,6-lutidine and/or 3,5-lutidine. 12. The preparation method according to claim 11, characterized in that in the step (A) benzoylation reaction, the mass/volume ratio of coli lactone to solvent _S1 is 1:1-100. 13. The preparation method according to claim 11, characterized in that in the step (A) benzoylation reaction, the solvent S ₁ is selected from dichloromethane and/or chloroform. 14. The preparation method according to claim 11, characterized in that in the step (A) benzoylation reaction, the base _B1 is selected from triethylamine and/or diisopropylethylamine. 15. The preparation method according to claim 11, characterized in that in the step (A) benzoylation reaction, the catalyst _C1 is selected from DMAP. 16. The preparation method according to claim 11, characterized in that in the step (A) benzoylation reaction, the molar ratio of coli lactone to base B ₁ , catalyst C ₁ and benzoyl chloride is 1: 2-4:0-1:2-4. 17. The preparation method according to claim 11, characterized in that in the step (A) benzoylation reaction, the post-treatment method is acid washing, alkali washing, and distilling off the solvent. 18. The preparation method according to claim 11, characterized in that: The solvent _S is selected from dichloromethane and/or chloroform; The base B _is selected from triethylamine and/or diisopropylethylamine; The catalyst C _is selected from DMAP; The mass/volume ratio of Cory lactone to solvent _S1 is 1:1-100; The molar ratio of coli lactone to base B ₁ , catalyst C ₁ and benzoyl chloride is 1:2-4:0-1:2-4. 19. The preparation method according to any one of claims 1-10, characterized in that the step (A) benzoylation reaction comprises: Mix coli lactone with solvent S ₁ , add base B ₁ and catalyst C ₁ , add benzoyl chloride dropwise at 0-40°C, and react for 5-20 hours at 0-40°C after the drop; after post-treatment to obtain The product Cory lactone dibenzoate; the mass/volume ratio of Cory lactone and solvent _S1 is 1:3-10; The molar ratio of Cory lactone to base B ₁ , catalyst C ₁ and benzoyl chloride is 1:1-1.5:0-1:2-3; solvent S ₁ is selected from dichloromethane and chloroform; base B ₁ is selected from Triethylamine and diisopropylethylamine; Catalyst C ₁ is DMAP; The post-treatment method is pickling, alkali washing, and then distilling off the solvent.