Methylprednisolone chemical synthesis method

Abstract

The present invention discloses the chemical synthesis process of methyl prednisoline. By using pregnenolone acetate as initial material, the present invention prepares methyl prednisoline through the steps of: epoxidation, mildew oxidation, place-11 reduction, place I and II dehydrogenation, place VI methylation and other reaction steps. The process of the present invention has mild reaction condition, high product purity, stable product quality, high product yield and low production cost, and is suitable for industrial production of methyl prednisoline.

Description

technical field [0001] The invention relates to a method for synthesizing methylprednisolone (1,4-pregnadiene-3,20-dione-11β, 17α, 21-triol-6α-methyl), which is based on Pregnidine dienolone acetate was used as starting material to prepare methylprednisolone. Background technique [0002] Methylprednisolone is the key intermediate for the production of the highly efficient glucocorticoid methylprednisolone sodium succinate. It has anti-inflammatory, anti-cellular immune effects and good curative effect. It is the first choice commonly used in the treatment of nephrotic syndrome medicine. [0003] At present, methylprednisolone is exclusively produced by U.S. Upjohn Company in foreign countries, and it has been monopolized by U.S. Upjohn Company for many years. There is no domestic industrialized manufacturer of methylprednisolone except our company, so downstream products and preparations have long relied on imports. [0004] Using pregnandienolone acetate as the starting...

AI Technical Summary

Problems solved by technology

In this method, the three key reaction processes of 11-position reduction, 1-2-position dehydrogenation reaction, and 6-position methylation are technically difficult, and the side reactions are difficult to control, resulting in poor product quality, low yield, and high cost. It is suitable for industrialization and industrial production without research and development

[0005] The specific problems in the process are: A. 11-position reduction There are two problems in this step reaction. One is that while the 11-position reduction is being carried out, the ketone groups at the 3 and 20 positions are also reduced, and there are many reaction by-products; the other is that the 11-position Incomplete bit reduction, thus affecting the yield and product quality

B. 1-2 position dehydrogenation reaction, selenium dioxide is used as a catalyst, the side reaction of the synthesis reaction is large, the yield is low, the catalyst is highly toxic, the post-treatment is difficult, and the waste water is difficult to treat, which affects the product quality and yield.

C. 6-position methylation synthesis reaction, the catalyst used is palladium calcium carbonate, reaction solvent ethanol, glacial acetic acid, the catalyst activity is poor, the reaction energy is low, causing the reactant to stay in the 6-7 position to form a double-bond conjugated system state, the methylation translocation is not complete, the reaction time is long and needs more than 8 hours, the quality of the reaction product is poor, and the yield is low

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