CN106632578B - Chloro- -6 β of 3 beta-hydroxy of 5 α -, 19 beta epoxide phytosterols - Google Patents

Chloro- -6 β of 3 beta-hydroxy of 5 α -, 19 beta epoxide phytosterols Download PDF

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CN106632578B
CN106632578B CN201610968114.4A CN201610968114A CN106632578B CN 106632578 B CN106632578 B CN 106632578B CN 201610968114 A CN201610968114 A CN 201610968114A CN 106632578 B CN106632578 B CN 106632578B
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CN106632578A (en
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王颖
尹传祥
宋长红
梁振峰
朱嘉震
王洪果
史峻嵩
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Shandong Ged Biotechnology Co Ltd
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    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
    • C07J71/0005—Oxygen-containing hetero ring

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Abstract

The present invention relates to one kind chloro- -6 β of 3 beta-hydroxy of 5 α -, 19 beta epoxide phytosterols and preparation method thereof.Chloro- -6 β of 3 beta-hydroxy of 5 α -; the preparation method of 19 beta epoxide phytosterols; the following steps are included: chloro- -6 β of 3 beta-hydroxy of 5 α -, the structure formula (IV) of 19 beta epoxide phytosterols is made by acylation reaction, addition reaction, epoxidation reaction in sterol.The present invention protects 3- hydroxyls using phytosterol cheap and easy to get as starting material, by acetylation, 5,6 additions then 6,19 epoxidations and obtain chloro- -6 β of 3 beta-hydroxy of 5 α -, 19 beta epoxide phytosterols.Starting material of the present invention is easy to get, high income and stabilization.

Description

5 α -chloro-3 β -hydroxy-6 β,19 β -epoxy phytosterols
(I) technical field
The invention belongs to the field of chemical industry, and particularly relates to 5 α -chloro-3 β -hydroxy-6 β,19 β -epoxy phytosterol and a preparation method thereof.
(II) background of the invention
The invention relates to an intermediate for preparing 19-hydroxy-4-androstenedione, 19-hydroxy-4-androstenedione is a very important steroid drug intermediate, and can be used for producing 19-hydroxy steroids, 19-demethyl steroid (19-norsteroid) drugs, such as 19-demethyl androstenedione (such as 19-demethyl-4-androstenedione and 19-demethyl-5 (10) -androstenedione), estrone, estradiol, estriol, norethindrone and derivatives, important 19-demethyl steroid intermediates such as mifepristone and drugs.
At present, the method for industrially producing 19-hydroxy-4-androstenedione uses diene (dehydroepiandrosterone) or dehydroepiandrosterone as a raw material and prepares the dehydroepiandrosterone through chemical reaction, for example, pregna-5, 16-diene-3-ol acetate (dehydroepiandrosterone acetate) is used as a raw material and is subjected to Beckmann rearrangement, addition reaction and oxidation of ketoxime to obtain 5 α -chloro-3 β -hydroxy-6 β and 19 β -epoxy phytosterol, and the method has multiple steps, high cost and low yield.
Patents CN102443038A and CN 104725460a disclose a method for synthesizing 19-hydroxy-4-androstenedione from dehydroepiandrosterone as a raw material, which has long reaction time and high production cost.
Therefore, although the industrial production of 19-hydroxyandrostenedione is realized by taking diene (dehydroepiandrosterone) or dehydroepiandrosterone as a raw material, the cost of the starting material is higher, namely 1300 yuan/kg of dehydroepiandrosterone, 2100 yuan/kg of dehydroepiandrosterone and only 130 yuan/kg of phytosterol, the project adopts phytosterol as the initial raw material, firstly synthesizes 5 α -chloro-3 β -hydroxy-6 β and 19 β -epoxy phytosterol intermediates, and then obtains the final product 19-hydroxy-4-androstenedione through one-step biological fermentation.
Disclosure of the invention
Based on the defects of the prior art, the invention provides 5 α -chloro-3 β -hydroxy-6 β,19 β -epoxy phytosterol and a preparation method thereof, and the preparation method has the advantages of few reaction steps, high product yield and low total cost.
The invention is realized by the following technical scheme:
the 5 α -chloro-3 β -hydroxy-6 β,19 β -epoxy phytosterol is characterized in that the structural formula is as follows:
because the phytosterol mainly comprises stigmasterol, β -sitosterol, campesterol and the like, R in the reaction formula is sterol alkane branched chain.
The preparation method of the 5 α -chloro-3 β -hydroxy-6 β,19 β -epoxy phytosterol comprises the following steps:
the sterol is subjected to acylation reaction, addition reaction and epoxidation reaction to obtain the structural formula (IV) of 5 α -chloro-3 β -hydroxy-6 β,19 β -epoxy phytosterol, wherein the reaction formula is as follows:
。
the method specifically comprises the following steps:
in the presence of a solvent, sterol and anhydride are subjected to acylation reaction to obtain a compound II, the compound II is subjected to reaction with a chlorinating agent in an organic solvent to obtain a compound III, and finally, the compound III is subjected to reaction with the chlorinating agent in the presence of a free radical initiator and illumination to obtain a compound 5 α -chloro-3 β -hydroxy-6 β,19 β -epoxy phytosterol IV.
Wherein,
in the acylation reaction, the sterol is low-cost phytosterol, and the sterol: the mass ratio of acid anhydride is 1: 1-10, the mass ratio of the sterol to the solvent is 1:5.5-7, and the reaction temperature is 80-95 ℃.
In the acylation reaction process, the solvent is toluene, and the acid anhydride is acetic anhydride.
The mass ratio of the compound II to the solvent in the addition reaction is 1: 15-18, the mass ratio of the compound II to the chlorinated reagent is 10:6-15, the chlorinated reagent is trichloroisocyanuric acid with higher yield and selectivity, and the solvent is acetone.
In the epoxidation reaction, the mass-to-volume ratio of the compound III to the solvent is 1W: 8V to 10V, and the reaction temperature is 80 ℃ to 90 ℃. The mass ratio of the solid compound III to the free radical initiator to the chlorinating agent is 10: 2.05-3.25: 8-15. The free radical initiator is preferably iodine and benzoyl peroxide in the mass ratio of 1.75-2.6 to 0.3-0.65. The solvent used was dichloroethane.
The preparation method of the 5 α -chloro-3 β -hydroxy-6 β,19 β -epoxy phytosterol comprises the following detailed steps:
firstly, in the condition of taking toluene as a solvent, phytosterol and acetic anhydride carry out acylation reaction to obtain a compound II:
secondly, reacting the compound II with trichloroisocyanuric acid in an organic solvent to obtain a compound III, wherein the solvent is acetone.
。
And finally, reacting the compound III with chlorinated agent N-chlorosuccinimide under the action of free radical initiator iodine and illumination to obtain a compound 5 α -chloro-3 β -hydroxy-6 β,19 β -epoxy phytosterol IV, wherein the used organic solvent is dichloroethane.
The acylation reaction process of the compound I is as follows: adding sterol into a toluene solvent, stirring for dissolving, then adding acetic anhydride, heating to 80-95 ℃, performing reflux reaction for 4-10h, performing TLC plate tracking reaction until the reaction is complete, then cooling to 55-65 ℃, adding water, stirring for 0.2-0.8h, standing for layering to remove a water phase (repeating for three times), performing organic phase vacuum distillation to recover toluene, distilling until the toluene is not discharged, adding an ethanol solution, pulping, stirring for 0.5-2h, cooling, filtering, leaching with ethanol, and drying to obtain a compound II;
the addition reaction process of the compound II comprises the following steps: dissolving a compound II in an organic solvent acetone, adding a small amount of water, stirring for 0.5-2h, cooling to-5-10 ℃, and dropwise adding a mixed solution of trichloroisocyanuric acid and acetone at the temperature, wherein the mass ratio of the compound II to the solvent acetone is 1: 15-18, 2-2.5 h, finishing dripping, controlling the temperature to react for 50 min-1 h, tracking the reaction by TLC (thin layer chromatography), adding 7-13% of sodium sulfite to stop the reaction, distilling under reduced pressure to recover acetone, distilling until the acetone is not discharged, adding water, stirring and pulping, 0.5-2h, filtering at 40-45 ℃, leaching with water, and drying to obtain a compound III;
the epoxidation reaction process of the compound III is as follows: dissolving a compound III into dichloroethane, wherein the mass-volume ratio of the compound III to the solvent is 1W: 8V to 10V, adding anhydrous sodium carbonate, iodine, benzoyl peroxide and N-chlorosuccinimide after stirring and dissolving uniformly, slowly raising the temperature to 80 ℃ to 90 ℃, reacting for 2 to 4 hours, observing the reaction phenomenon and tracking the reaction completely by TLC, cooling to room temperature, adding water, stirring for 0.2 to 0.8 hour, standing for layering, washing an organic layer by 7 to 13 percent sodium thiosulfate, standing for layering to remove a water layer, washing by water, standing for layering, distilling the organic phase under reduced pressure, recovering dichloroethane, distilling until the dichloroethane can not be discharged, and drying to obtain a compound IV. Wherein the mass ratio of the solid compound (III), the anhydrous sodium carbonate, the iodine, the benzoyl peroxide and the N-chlorosuccinimide is 10:5-7:1.75-2.6: 0.3-0.65: 8-15.
The invention has the beneficial effects that the invention takes cheap and easily obtained phytosterol as the starting material, and 5 α -chloro-3 β -hydroxy-6 β and 19 β -epoxy phytosterol is obtained by acetylation protection of 3-hydroxy, 5-addition of 6-position and then 6-position and 19-position epoxidation.
(IV) detailed description of the preferred embodiments
Example 1
Acylation reaction:
adding 150ml of toluene into a 500ml three-mouth reaction bottle, adding 20g of solid sterol while stirring, then adding 20ml of acetic anhydride, heating to 80-95 ℃ for reflux reaction for 7h, sampling TLC (thin layer chromatography) plate analysis until the reaction is completed, cooling with cold water to 55 ℃, adding 20ml of water, stirring for 0.5h, standing for layering, removing a water phase, washing an organic phase twice with 20ml of water respectively, distilling the organic phase under reduced pressure to recover the toluene until the toluene is not discharged, adding 75ml of absolute ethyl alcohol, pulping, stirring for 1h, then cooling to 10 ℃ for filtering, leaching with 10ml of absolute ethyl alcohol, drying to obtain 21.5g of a solid compound (II), wherein the yield is 98%.
Addition reaction:
adding 300ml of acetone into a 1000ml three-mouth reaction bottle, adding 20g of solid compound (II) while stirring, adding 30ml of water, stirring for 1h, cooling to 0 ℃, slowly dripping into a mixed solution of 16g of trichloroisocyanuric acid and 80ml of acetone for 2h, then controlling the temperature to react for 50min, stopping the reaction by using 50ml of 10% sodium sulfite after the TLC point plate completely reacts, and then heating to 30 ℃ to distill and recover the acetone under reduced pressure. Steaming until acetone is not discharged, adding 400ml of water, heating to 40 ℃, stirring, pulping for 1h, filtering, leaching with 100ml of water, and flood-drying to obtain 21.5g of the solid compound (III), wherein the yield is 96%.
Epoxidation reaction:
adding 100ml of dichloroethane into a 500ml three-mouth reaction bottle, adding 10g of the solid compound (III) under stirring, stirring for 0.5h, adding 6g of anhydrous sodium carbonate, 2.25g of iodine, 0.37g of benzoyl peroxide and 10g of N-chlorosuccinimide, slowly heating to 80-90 ℃, reacting for 3h, cooling to room temperature after TLC plate-on reaction is completed, adding 40g of water for washing, stirring for 0.5h for static demixing, washing an organic layer for 1-1.5 h by 40ml of 10% sodium thiosulfate, statically demixing, washing the organic phase by 10% of organic phase weight, statically demixing, distilling the organic layer under reduced pressure and recovering the dichloroethane. Distillation was carried out until no more, and drying was carried out to obtain 8.2g of a solid compound (IV) in a yield of 82%.
Example 2
Acylation reaction:
adding 187.5 ml of toluene into a 500ml three-mouth reaction bottle, adding 25g of solid sterol while stirring, then quickly dropping 25ml of acetic anhydride, slowly heating to 95 ℃ for reflux reaction for 7 hours, sampling TLC (thin layer chromatography) plate analysis until the reaction is completed, cooling to 55 ℃ with cold water, adding 25ml of water, stirring for 0.5 hour, standing for layering, removing a water phase, washing an organic phase twice with 25ml of water respectively, recovering the solvent toluene by organic phase vacuum distillation, recovering the solvent toluene until the toluene is not discharged, and drying to obtain 26.8g of a solid compound (II), wherein the yield is 97.5%.
Addition reaction:
adding 150ml of acetone and 10g of solid compound (II) into a 500ml three-mouth reaction bottle, uniformly stirring, adding 15ml of water, continuously stirring for 1h, cooling to-5 ℃ by using brine ice, slowly dropwise adding a mixed solution of 13g of trichloroisocyanuric acid and 50ml of acetone, keeping the temperature for 2.5h, dropwise adding, then controlling the temperature to react for 55min, stopping the reaction by using 25ml of 10% sodium sulfite after the TLC point plate reaction is completed, adding 20ml of water into the reaction bottle, stirring and pulping for 1h at 40 ℃, performing suction filtration, leaching by using 50ml of water, and drying to obtain 10.5g of solid compound (III), wherein the yield is 95%.
Epoxidation reaction:
adding 140ml of dichloroethane and 15g of solid compound (III) into a 500ml three-mouth reaction bottle, stirring for 30min, adding 9g of anhydrous sodium carbonate, 2.88g of iodine, 0.88g of benzoyl peroxide and 19g of N-chlorosuccinimide, heating to 84 ℃, carrying out reflux reaction for 3g, reducing the temperature to 30 ℃ after TLC plate reaction is completed, adding 60g of water for washing, washing for 30min for static delamination, washing an organic layer for 1h by 60ml of 10% sodium thiosulfate, carrying out static delamination, washing an organic phase by 60ml of water, carrying out reduced pressure distillation on the organic phase after delamination, recovering the dichloroethane, steaming until no dichloroethane is obtained, drying to obtain 12.1g of solid compound (IV), and the yield is 81.5%.
Example 3
Acylation reaction:
adding 126ml of toluene into a 500ml three-mouth reaction bottle, adding 20g of solid sterol while stirring, then adding 92.5ml of acetic anhydride, heating to 80 ℃ for reflux reaction for 10 hours, sampling TLC (thin layer chromatography) plate analysis until the reaction is complete, cooling to 60 ℃ with cold water, adding 20ml of water, stirring for 0.8 hour, standing for layering, removing a water phase, washing an organic phase with 25ml of water for three times respectively, distilling the organic phase under reduced pressure to recover the toluene, distilling until the toluene is not discharged, adding 75ml of absolute ethyl alcohol, pulping, stirring for 0.5 hour, then cooling to 15 ℃ for filtering, leaching with 15ml of absolute ethyl alcohol, and drying to obtain a solid compound (II), wherein the yield is 97%.
Addition reaction:
379ml of acetone is added into a 1000ml three-mouth reaction bottle, 20g of solid compound (II) is added under stirring, 37ml of water is added and stirred for 2 hours, the temperature is reduced to-5 ℃, the mixture of 12g of trichloroisocyanuric acid and 80ml of acetone is slowly dripped in the mixture for 3 hours, then the temperature is controlled and the reaction is carried out for 60 minutes, 7% of sodium sulfite 71ml is used for stopping the reaction after the TLC point plate reaction is completed, and then the temperature is increased to 35 ℃ for reduced pressure distillation and recovery of acetone. Steaming until acetone is not discharged, adding 400ml of water, heating to 43 ℃, stirring, pulping for 1h, filtering, leaching with 100ml of water, and flood-drying to obtain a solid compound (III), wherein the yield is 96%.
Epoxidation reaction:
adding 90ml of dichloroethane into a 500ml three-mouth reaction bottle, adding 10g of solid compound (III) under stirring, stirring for 0.5h, adding 5g of anhydrous sodium carbonate, 2.6g of iodine, 0.3g of benzoyl peroxide and 8g of N-chlorosuccinimide, slowly heating to 80 ℃, reacting for 4h, cooling to room temperature after TLC plate-spotting reaction is completed, adding 45g of water for washing, stirring for 0.8h for static demixing, washing an organic layer for 1-1.5 h by 58ml of 7% sodium thiosulfate, statically demixing, washing the organic phase by 15% of organic phase weight, statically demixing, distilling the organic layer under reduced pressure and recovering dichloroethane. Distilling till the product can not be obtained, and drying to obtain a solid compound (IV) with the yield of 84%.
Example 4
Acylation reaction:
adding 187.5 ml of toluene into a 500ml three-mouth reaction bottle, adding 25g of solid sterol while stirring, then quickly dropping 231ml of acetic anhydride, slowly heating to 90 ℃ for reflux reaction for 4 hours, sampling TLC (thin layer chromatography) spot plate analysis until the reaction is completed, cooling to 65 ℃ with cold water, adding 25ml of water, stirring for 0.2 hour, standing for layering, removing a water phase, washing an organic phase twice with 30ml of water respectively, recovering the solvent toluene by organic phase vacuum distillation, recovering the solvent toluene until the toluene is not discharged, and drying to obtain a solid compound, wherein the yield is 98.1%.
Addition reaction:
adding 130ml of acetone and 10g of solid compound (II) into a 500ml three-mouth reaction bottle, stirring uniformly, adding 20ml of water, continuing stirring for 0.5h, cooling to 10 ℃ with brine ice, slowly dropwise adding a mixed solution of 15g of trichloroisocyanuric acid and 61ml of acetone, keeping the temperature for 2.5h, then controlling the temperature to react for 50min, stopping the reaction by using 19ml of 13% sodium sulfite after the TLC point plate reaction is completed, adding 25ml of water into the reaction bottle, stirring and pulping at 45 ℃ for 2h, performing suction filtration, leaching by using 60ml of water, and drying to obtain the solid compound, wherein the yield is 96.3%.
Epoxidation reaction:
adding 120ml of dichloroethane and 15g of solid compound (III) into a 500ml three-mouth reaction bottle, stirring for 25min, adding 10.5g of anhydrous sodium carbonate, 2.62g of iodine, 0.98g of benzoyl peroxide and 22.5g of N-chlorosuccinimide, heating to 90 ℃ for reflux reaction for 2h, cooling to 25 ℃ after TLC plate-spotting reaction is completed, adding 65g of water for washing, washing for 0.2h for static layering, washing an organic layer for 0.8h by using 47ml of 13% sodium thiosulfate, standing for layering, washing an organic phase by using 55ml of water, after layering, distilling the organic phase under reduced pressure, recovering the dichloroethane, steaming until the dichloroethane is not discharged, and drying to obtain the solid compound (IV) with the yield of 83.2%.
Example 5
Acylation reaction:
adding 201ml of toluene into a 500ml three-mouth reaction bottle, adding 25g of solid sterol while stirring, then quickly dropping 46ml of acetic anhydride, slowly heating to 95 ℃ for reflux reaction for 5 hours, cooling with cold water to 55 ℃ after TLC (thin layer chromatography) plate sampling analysis is completed, adding 20ml of water, stirring for 0.4 hour, standing for layering, removing a water phase, washing an organic phase twice with 35ml of water respectively, carrying out vacuum distillation on the organic phase to recover the solvent toluene until toluene is not produced, and drying to obtain a solid compound with the yield of 98.3%.
Addition reaction:
adding 160ml of acetone and 10g of solid compound (II) into a 500ml three-mouth reaction bottle, stirring uniformly, adding 20ml of water, continuing stirring for 1.5h, cooling to 5 ℃ with ice brine, slowly dropwise adding a mixed solution of 10g of trichloroisocyanuric acid and 57ml of acetone, keeping the temperature for 2h, dropwise adding, then controlling the temperature to react for 55min, stopping the reaction by using 27ml of 10% sodium sulfite after TLC point plate reaction is completed, adding 27ml of water into the reaction bottle, stirring and pulping at 42 ℃ for 1h, performing suction filtration, rinsing by using 60ml of water, and drying to obtain the solid compound with the yield of 96.2%.
Epoxidation reaction:
adding 135ml of dichloroethane and 15g of solid compound (III) into a 500ml three-mouth reaction bottle, stirring for 20min, adding 9g of anhydrous sodium carbonate, 3g of iodine, 0.75g of benzoyl peroxide and 15g of N-chlorosuccinimide, heating to 85 ℃, carrying out reflux reaction for 2h, reducing the temperature to 28 ℃ after TLC plate reaction is completed, adding 70g of water for washing, washing for 0.5h for static delamination, washing an organic layer for 0.6h by 55ml of 10% sodium thiosulfate, carrying out static delamination, washing an organic phase by 55ml of water, carrying out decompression distillation on the organic phase after delamination, recovering the dichloroethane, steaming until the dichloroethane is not discharged, and drying to obtain the solid compound (IV) with the yield of 83.8%.

Claims (3)

1. A preparation method of 5 α -chloro-3 β -hydroxy-6 β,19 β -epoxy phytosterol is characterized in that the structural formula of the 5 α -chloro-3 β -hydroxy-6 β,19 β -epoxy phytosterol Is (IV),wherein R is a sterol alkane branch;
the preparation method of the 5 α -chloro-3 β -hydroxy-6 β,19 β -epoxy phytosterol comprises the following steps:
subjecting sterol to acylation reaction, addition reaction and epoxidation reaction to obtain structural formula (IV) of 5 α -chloro-3 β -hydroxy-6 β,19 β -epoxy phytosterol;
the method specifically comprises the following steps:
carrying out acylation reaction on sterol and anhydride under the action of a solvent to obtain a compound II, reacting the compound II with a chlorinating agent under the action of an organic solvent to obtain a compound III, and finally reacting the compound III with the chlorinating agent under the action of a free radical initiator and illumination to obtain a compound 5 α -chloro-3 β -hydroxy-6 β,19 β -epoxy phytosterol IV;
wherein: in the acylation reaction, sterol: the mass ratio of acid anhydride is 1: 1-10, wherein the mass ratio of the sterol to the solvent is 1:5.5-7, and the reaction temperature is 80-95 ℃;
the mass ratio of the compound II to the solvent in the addition reaction is 1: 15-18, wherein the mass ratio of the compound II to the chlorinated reagent is 10: 6-15;
in the epoxidation reaction, the mass-to-volume ratio of the compound III to the solvent is 1W: 8V to 10V, and the reaction temperature is 80 ℃ to 90 ℃; the mass ratio of the solid compound III to the free radical initiator to the chlorinating agent is 10: 2.05-3.25: 8-15 parts of; in the epoxidation reaction, the free radical initiator is iodine and benzoyl peroxide, and the mass ratio of the free radical initiator to the benzoyl peroxide is 1.75-2.6: 0.3-0.65;
in the acylation reaction, sterol is phytosterol, solvent is toluene, and acid anhydride is acetic anhydride;
in the addition reaction, the chlorinated reagent is trichloroisocyanuric acid, and the solvent is acetone;
in the epoxidation reaction, when a compound IV is synthesized, a used solvent is dichloroethane;
the acylation reaction process of the compound I is as follows: adding sterol into a toluene solvent, stirring and dissolving, then adding acetic anhydride, heating to 80-95 ℃, carrying out reflux reaction for 4-10h, carrying out TLC point plate tracking reaction until the reaction is complete, then cooling to 55-65 ℃, adding water, stirring for 0.2-0.8h, standing for layering to remove a water phase, carrying out organic phase vacuum distillation to recover toluene, distilling until toluene is not discharged, adding an ethanol solution, pulping, stirring for 0.5-2h, cooling, filtering, leaching with ethanol, and drying to obtain a compound II;
the addition reaction process of the compound II comprises the following steps: dissolving a compound II in an organic solvent acetone, adding a small amount of water, stirring for 0.5-2h, cooling to-5-10 ℃, and dropwise adding a mixed solution of trichloroisocyanuric acid and acetone at the temperature, wherein the mass ratio of the compound II to the solvent acetone is 1: 15-18, 2-2.5 h, finishing dripping, controlling the temperature to react for 50 min-1 h, tracking the reaction by TLC completely, adding a sodium sulfite solution to stop the reaction, distilling under reduced pressure to recover acetone, distilling until the acetone is not discharged, adding water, stirring and pulping, filtering for 0.5-2h at 40-45 ℃, leaching with water, and drying to obtain a compound III;
the epoxidation reaction process of the compound III is as follows: dissolving a compound III into dichloroethane, wherein the mass-volume ratio of the compound III to the solvent is 1W: 8V to 10V, adding anhydrous sodium carbonate, iodine, benzoyl peroxide and N-chlorosuccinimide after stirring and dissolving uniformly, slowly raising the temperature to 80 ℃ to 90 ℃, reacting for 2 to 4 hours, observing the reaction phenomenon and tracking the reaction completely by TLC, cooling to room temperature, adding water, stirring for 0.2 to 0.8 hour, standing for layering, washing an organic layer with a sodium thiosulfate solution, standing for layering to remove a water layer, washing with water, standing for layering, distilling the organic phase under reduced pressure, recovering dichloroethane, distilling until the dichloroethane is not discharged, and drying to obtain a compound IV.
2. The process for preparing 5 α -chloro-3 β -hydroxy-6 β,19 β -epoxy phytosterol according to claim 1, wherein the mass ratio of the solid compound III, anhydrous sodium carbonate, iodine, benzoyl peroxide and N-chlorosuccinimide is 10:5-7:1.75-2.6: 0.3-0.65: 8-15 in the epoxidation reaction of the compound III.
3. The process for preparing 5 α -chloro-3 β -hydroxy-6 β,19 β -epoxy phytosterol according to claim 2, wherein the mass concentration of the sodium sulfite solution and the mass concentration of the sodium thiosulfate solution are both 7-13%.
CN201610968114.4A 2016-10-31 2016-10-31 Chloro- -6 β of 3 beta-hydroxy of 5 α -, 19 beta epoxide phytosterols Active CN106632578B (en)

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