Preparation method of high-purity hydrocortisone

A technology of hydrocortisone and hydrocortisone acetate, which is applied in the direction of organic chemistry and steroids, can solve the problems of unfriendly environment, low yield, high toxicity, etc., and achieve low requirements for reaction devices and improve product quality. The effect of purity and good market prospects

Active Publication Date: 2020-08-11
ZHEJIANG SHENZHOU PHARMA
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0007] The above two chemical synthesis routes all have problems such as that the above-mentioned route is longer, and all need to use iodine that is more toxic and environmentally unfriendly in the reaction process, and more impurities will be generated in the upper iodine substitution process, which is difficult to remove. Suitable for industrial production
[0008] Another biosynthesis method can overcome the problems of the above-mentioned chemical synthesis method that the reaction route is too long, there are many impurities and easy to produce pollution, and is widely welcomed, but the yield of this method is not high, and it is still in the stage of further research

Method used

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Embodiment 1

[0026] Embodiment 1 A kind of preparation method of high-purity hydrocortisone comprises the steps:

[0027] 1) Bromohydrin reaction: 50 grams of 17α-hydroxypregna-4,9(11)-diene-3,20-dione-21-acetate (1) was added to 300 ml of acetone, and the mass concentration was 5 % perchloric acid aqueous solution 70 milliliters, be cooled to 5 ℃, add N-bromosuccinimide 25 grams, stir reaction, after reaction is finished, neutralize with the sodium sulfite aqueous solution of 5% mass concentration, concentrate organic solvent, water Analyze, filter, obtain 66 grams of intermediate (2).

[0028] 2) Debromination reaction: under nitrogen protection, 66 grams of intermediate (2) were dissolved in 130 milliliters of N,N-dimethylformamide and 300 milliliters of tetrahydrofuran, and 33 milliliters of thioglycolic acid, 40 grams of zinc powder and 2 grams of hexahydrate were added Chromium trichloride, control temperature 5 ℃ of stirring reactions, after reaction is finished, neutralize with th...

Embodiment 2

[0030] Embodiment 2 A kind of preparation method of high-purity hydrocortisone comprises the steps:

[0031] 1) Bromohydrin reaction: 50 grams of 17α-hydroxypregna-4,9(11)-diene-3,20-dione-21-acetate (1) was added to 1500 milliliters of acetone at a mass concentration of 10 50 milliliters of fluoroboric acid aqueous solution, be cooled to-5 ℃, add 60 grams of dibromodimethylhydantoin and stir reaction, after reaction is finished, be neutralized with the sodium carbonate aqueous solution that mass concentration is 10%, condense organic solvent, water analysis , and filtered to obtain 67 g of intermediate (2).

[0032]2) Debromination reaction: under nitrogen protection, 67 grams of intermediate (2) was dissolved in 300 milliliters of dimethyl sulfoxide and 500 milliliters of 2-methyltetrahydrofuran, and 14 milliliters of thioglycolic acid, 15 grams of zinc powder and 3 grams of hexahydrate were added Chromium trichloride, control the temperature-5 ℃ of stirring reaction, after...

Embodiment 3

[0034] Embodiment 3 A kind of preparation method of high-purity hydrocortisone comprises the steps:

[0035] 1) Bromo-hydroxyl reaction: 50 grams of 17α-hydroxypregna-4,9(11)-diene-3,20-dione-21-acetate (1) was added to 1000 milliliters of methyl ethyl ketone, and the mass concentration was 25 milliliters of 30% methanesulfonic acid aqueous solution is cooled to 0 DEG C, add 45 grams of dibromodimethylhydantoin, stir and react, after the reaction is completed, neutralize with ammonia water of 30% mass concentration, concentrate the organic solvent, water analysis, After filtration, 65 g obtained Intermediate 2.

[0036] 2) Debromination reaction: under nitrogen protection, 65 grams of intermediate (2) was dissolved in 200 milliliters of N,N-dimethylformamide and 750 milliliters of acetone, and 70 milliliters of thioglycolic acid, 65 grams of zinc powder and 6.5 grams of hexahydrate were added Chromium trichloride, 10 ℃ of stirring reactions of control temperature, after the c...

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Abstract

The invention discloses a preparation method of high-purity hydrocortisone, and belongs to the technical field of preparation and processing of medicines. According to the method, 17alpha-hydroxypregna-4, 9 (11)-diene-3, 20-diketone-21-acetate is used as a starting material, and the high-purity hydrocortisone is prepared through three steps of bromo-hydroxyl, debromination and hydrolysis. According to the preparation method of the high-purity hydrocortisone disclosed by the invention, the reaction process can be effectively shortened by improving the defects of a traditional process, the generation of impurities during the reaction process is controlled, the use of iodine with characteristics of high toxicity and environmental unfriendliness is avoided, the environmental pollution is reduced, and the method has characteristics of high overall conversion rate, simple operation and wide market prospect, and is suitable for industrial production.

Description

technical field [0001] The invention relates to the technical field of medicine preparation, in particular to a preparation method of high-purity hydrocortisone. Background technique [0002] Hydrocortisone and its derivatives are a class of adrenocortical hormone drugs with high activity and effects on glucose metabolism, anti-inflammation, anti-allergy and anti-shock. Its products include hydrocortisone and hydrocortisone acetate , Hydrocortisone sodium phosphate, etc. Such products are widely used in the treatment of adrenal insufficiency, rheumatoid disease, lupus erythematosus, bronchial asthma, dermatitis and other allergic diseases, and have broad market prospects. [0003] At present, the preparation of hydrocortisone mainly includes chemical synthesis and biosynthesis. The chemical synthesis method has the problems that the reaction route is too long, the reaction process is complicated, the impurities are too many, and pollution is easy to occur. For example: 1) Z...

Claims

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Application Information

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IPC IPC(8): C07J5/00
CPCC07J5/0053
Inventor 邵振平王荣陈克纲王炳乾王友富
Owner ZHEJIANG SHENZHOU PHARMA
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