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Method for synthesizing clobetasol propionate intermediate

A technology of clobetasol propionate and betamethasone, which is applied in the directions of steroids, organic chemistry, etc., can solve the problems of long process route, large solvent pollution, many influencing factors, etc., and achieves good application prospects and less environmental pollution. , the effect of improving the overall technical level

Active Publication Date: 2013-05-01
ZHEJIANG XIANJU XIANLE PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, its process route is long, there are many influencing factors, and there are many side reactions.
Moreover, the solvent used is highly polluted and difficult to recycle

Method used

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  • Method for synthesizing clobetasol propionate intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Dissolve 20 g of betamethasone 17-esterified product obtained by hydrolysis of betamethasone through cyclic ester in 150 ml of acetone, stir and dissolve fully, add 6 g of ZnCl 2 , after heating up to 35°C, add 30g of BTC. After passing through the BTC, keep it warm for 3 hours. After the reaction, concentrate under reduced pressure at a temperature of 40°C until the solution contains 30ml of acetone, and then add 300ml of acetone The drinking water was analyzed, filtered, and finally dried at a temperature of 80° C. for 16 hours to obtain 19.64 g of a crude product of clobetasol propionate. The yield was 98.2%, and the crude product content of clobetasol propionate was analyzed to be 96.9%.

Embodiment 2

[0036] Dissolve 20 g of betamethasone 17-esterified product obtained by hydrolysis of betamethasone through cyclic ester in 150 ml of acetone, stir and dissolve fully, then add 7.2 g of FeCl 3 , after heating up to 30°C, add 24g of BTC. After passing through the BTC, keep it warm for 2 hours. After the reaction, concentrate under reduced pressure at a temperature of 35°C until the solution contains 20ml of acetone, and then add 300ml The drinking water was analyzed, filtered, and finally dried at a temperature of 85° C. for 10 hours to obtain 19.5 g of a crude product of clobetasol propionate. The yield was 97.5%, and the crude product content of clobetasol propionate was analyzed to be 95.6%.

Embodiment 3

[0038] Dissolve 20 g of betamethasone 17-esterified product obtained by hydrolysis of betamethasone through cyclic ester in 150 ml of acetone, stir and dissolve fully, then add 4 g of AlCl 3After heating up to 35°C, add 28g of BTC. After passing through the BTC, keep it warm for 4 hours. After the reaction, concentrate under reduced pressure at a temperature of 30°C until the solution contains 20ml of acetone, and then add 300ml The drinking water was analyzed, filtered, and finally dried at a temperature of 75° C. for 18 hours to obtain 19.62 g of a crude product of clobetasol propionate. The yield was 98.1%, and the crude product content of clobetasol propionate was analyzed to be 95.8%.

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Abstract

The invention discloses a method for synthesizing clobetasol propionate, which belongs to the technical field of synthesis of steroid medicaments in the pharmaceutical chemistry and comprises the following steps: (1) dissolving betamethasone-17-ester into acetone solution; (2) adding a catalyst and BTC (bis(trichloromethyl) carbonate) for carrying out chloroacetic reaction at the reaction temperature of 30-50DEG C for 2-5 hours; and (3) after reaction, carrying out reduced pressure concentration, elutriation, filtering and drying. Compared with the traditional process, the yield can be improved by 6 percent, the cost is reduced by 20 percent and the quality is remarkably improved. The using amount of original auxiliary materials are reduced by 20 percent, the using amount of a toxic material of methanesulfonyl chloride can be reduced by 1 ton each year, the using amount of DMF (Dimethyl Formamide) can be reduced by 17 tons and the using amount of pyridine can be reduced by 6.3 tons, the economic cost can be totally saved by 366,000 yuan and waste water drain can be reduced by 310tons / year; and in addition, the invention greatly reduces the pressure for protecting the environment and can effectively reduce the hazard on human body and the pollution on the environment.

Description

technical field [0001] The invention belongs to the technical field of steroid medicine synthesis in medicinal chemistry, and in particular relates to a synthesis method of a clobetasol propionate intermediate. Background technique [0002] Clobetasol propionate, its structural formula (formula (1)), is a potent halogen-containing adrenocorticosteroid drug with strong anti-inflammatory, anti-pruritic and vasoconstrictive effects, and its anti-inflammatory effect is about that of hydrocortisone It is also used externally to treat neurodermatitis, contact dermatitis, eczema, discoid lupus erythematosus and other symptoms and is currently widely used clinically. It has been very popular in the international market, ranking the top among hormones. At present, there are only a few domestic companies in normal production, and the total yield is about 88%. [0003] [0004] Formula 1). [0005] The process route for producing synthetic clobetasol propionate is complex, techni...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07J7/00
Inventor 张和明张平
Owner ZHEJIANG XIANJU XIANLE PHARMA