Preparation method of cortisone acetate

Abstract

The invention relates to a preparation method of cortisone acetate. Anecortave acetate is used as a raw material and sequentially takes addition, oxidization and reduction reaction to obtain the anecortave acetate. The method comprises the following reaction steps of A, addition reaction: under the nitrogen production, adding the anecortave acetate into an organic solvent; adding a halogenating reagent and an acid catalyst to obtain an intermediate II; B, oxidization reaction: under the nitrogen gas protection, adding the compound II into the organic solvent; adding an oxidizing agent to obtain an intermediate III; C, reduction reaction: under the nitrogen gas production, adding the compound III into the organic solvent; adding an acid catalyst and a reducing agent to obtain a target product of the cortisone acetate IV. The method has the advantages that the raw materials can be easily obtained; the reaction steps are few; the quality and the yield achieve the obvious competitiveness; in addition, the pollution on the environment is reduced.

Description

technical field [0001] The invention relates to a preparation method of medicine, in particular to a preparation method of cortisone acetate, which belongs to the technical field of biopharmaceuticals. Background technique [0002] Cortisone Acetate (Cortisone Acetate), also known as corticosterone acetate (Adreson), is a steroid hormone It is an important intermediate in the class of APIs, and can be used to synthesize various high value-added APIs such as prednisone acetate and hydrocortisone. At present, it is recorded in Chinese, American and European pharmacopoeias. Cortisone acetate is a medium-acting adrenal cortex hormone drug, which acts on glucose metabolism and has a certain impact on electrolyte metabolism. For severe bronchial asthma, severe dermatitis and other allergic diseases, active rheumatism, rheumatoid arthritis, lupus erythematosus and other diseases. [0003] The preparation method of traditional cortisone acetate is carried out with reference to the...

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Problems solved by technology

[0003] The preparation method of traditional cortisone acetate is carried out with reference to the process of cortisone acetate in the "National Compilation of Raw Materials Processes" (State Administration of Medicine, 1980), specifically by 16α, 17α-ring Oxyprogesterone first oxidizes α-OH (11α-hydroxyl-16α, 17α-epoxyprogesterone) on C11 Rhizopus niger, then oxidizes α-OH on C11 with chromic anhydride to ketone group, and then bromines and removes Cortisone acetate is obtained by bromine, iodine, and replacement. This synthetic route has long steps, low yield, and poor quality. At the same time, the reaction involves dangerous hydrogenation operations, which requires high production environment and equipment. Iodine is used in the process of the 21-position side chain, the price is high, and a large amount of iodine-containing wastewater is produced at the same time, which is more serious to environmental pollution. At the same time, due to the existence of the 11-position carbonyl group, the selectivity in the process of adding iodine is poor, and there are many side reactions. Both quality and yield are deficient

Chinese patents CN201210496816.9 and CN201410150052.7 relate to the synthesis of cortisone acetate intermediates and cortisone acetate, which use 4-pregnene-11α, 17α-dihydroxy-3,20-dione as raw materials. Cortisone acetate is prepared by oxidation, iodine addition, replacement and other reactions. Although the synthesis steps of the above route are short, the starting material needs to undergo biological fermentation, and the fermentation process is more complicated. At the same time, the reaction still uses iodine, which still has high cost and waste water volume. big problem

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