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Prednisolone acetate preparation method

A prednisolone acetate, reaction technology, applied in the direction of steroids, organic chemistry, etc., can solve the problems of high production cost, unfavorable production, and potential safety hazards of prednisolone acetate, so as to shorten the production cycle and reduce the Solubility, effect of increasing stability

Inactive Publication Date: 2016-04-20
HUAZHONG PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0014] Chinese patent CN201310348285.3 adopts the above-mentioned process route to prepare prednisolone acetate. This preparation method avoids the use of metal chromium and elemental iodine, and the stability of the intermediate is also improved; Heavy metals are introduced into the process, and the low-boiling solvent diethyl ether needs to be used in multi-step reactions such as reduction, bromination, and replacement, which is not conducive to production in summer when the temperature is high, and there are great safety hazards
[0017] Chinese patent CN00136583.5 adopts the above-mentioned process route to prepare the prednisolone acetate intermediate reduction product. The preparation process adopts the two-step reaction of semicarbazone protection and reduction to complete in a "one-pot method", but the patent method does not mention the whole The key step of the process route is the deprotection reaction
The greater solubility of the reaction product in the deprotection process in the acidic solvent system and the increased resin hydrolysis step will inevitably affect the yield level of the process. The total yield of the two-step reaction mass of nitrosation and resin hydrolysis in the deprotection process is only 55% to 60%. %, the short board of the yield of this process makes the production cost of prednisolone acetate remain high

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] Add 750ml of acetone, 30g of prednisolone acetate intermediate reduction, 12g of sodium acetate, 50ml of acetic anhydride, and 8ml of acetic acid into the reaction flask in sequence, and heat up and reflux for 4 hours. TLC showed that the reaction was complete. Most of the solvent was recovered by atmospheric distillation, and then evaporated to dryness under reduced pressure, cooled to below 5°C, stirred for 30 minutes, left to stand for more than 2 hours, filtered, and dried to obtain 32.0 g of esterified product.

[0040] Put 30g of the esterified product into a solution prepared by 150ml of 36% hydrochloric acid, 240ml of water, and 15ml of chloroform, and stir at 25°C to 30°C for 30 minutes to dissolve. Cool down, and add dropwise a solution prepared from 30 g of sodium nitrite and 1050 ml of water at 18°C ​​to 22°C. After the addition was complete, the reaction was continued at 18°C ​​to 22°C for 3 hours. TLC showed that the reaction was complete, lower the tempe...

Embodiment 2

[0042] Add 750ml of acetone, 30g of prednisolone acetate intermediate reduction, 15g of potassium acetate, 51ml of acetic anhydride, and 9ml of acetic acid into the reaction flask in sequence, and heat up and reflux for 4.5 hours. TLC showed that the reaction was complete, most of the solvent was recovered by atmospheric distillation, and then the solvent was evaporated under reduced pressure, cooled to below 5°C, stirred for 30 minutes, left to stand for more than 2 hours, filtered, and dried to obtain 31.9g of esterified product.

[0043] Put 30g of the esterified product into a solution prepared by 150ml of 36% hydrochloric acid, 240ml of water, and 15ml of chloroform, and stir at 25°C to 30°C for 30 minutes to dissolve. Cool down, and add dropwise a solution prepared from 30 g of sodium nitrite and 1050 ml of water at 18°C ​​to 22°C. After the addition was complete, the reaction was continued at 18°C ​​to 22°C for 3 hours. TLC showed that the reaction was complete, lower ...

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Abstract

The present invention relates to a prednisolone acetate preparation method which is as follows: prednisolone acetate can be obtained by successive 3-site and 20-site keto-protection reaction, 11-site keto-reduction reaction, 21-site hydroxyl esterification reaction and 3-site and 20-site keto-deprotection reaction of prednisone acetate as a raw material. A new synthetic route of first esterification and then deprotection is provided, nitrosification quenching reaction and resin hydrolysis reaction can be omitted in the deprotection step, the technical process is greatly simplified, the cost of production is reduced, and the method is suitable for mass production.

Description

technical field [0001] The invention belongs to the field of chemical pharmacy, and in particular relates to a preparation method of prednisolone acetate. Background technique [0002] The structural formula of prednisolone acetate (11β, 17α, 21-trihydroxypregna-1,4-diene-3,20-dione-21-acetate) is: [0003] [0004] Prednisolone acetate is a glucocorticoid drug, which can be used externally to treat allergic, non-infectious skin diseases and some proliferative skin diseases, and can also be used to treat allergic and autoimmune inflammatory diseases, collagen diseases, etc. Prednisolone acetate is an important intermediate for the synthesis of prednisolone and other steroid drugs, and is widely used in the field of steroid drugs. [0005] The traditional preparation method of prednisolone acetate is divided into biotransformation and chemical synthesis, specifically: [0006] ⑴, with hydrocortisone acetate as the conversion substrate, the Arthrobacter fermentation metho...

Claims

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Application Information

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IPC IPC(8): C07J5/00
CPCC07J5/0053
Inventor 廖俊付林曾建华李桂莲曾纬王勇
Owner HUAZHONG PHARMA
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