Process of preparation of flumethasone 21-acetate, or flumethasone and its 17-carboxyl androsten analogue

摘要

A process for the preparation of high purity flumethasone in high yield involves C3 protecting 9,11-epoxy-17,21-dihydroxy-16-methylpregna-1,4-diene-3,20-dione,21-acetate, fluorinating at 6, removing the C3 protecting group, fluorinating the 9,11-epoxy group. The resulting flumethasone 21-acetate is treated with the methanolic potassium hydroxide in the presence of an oxidation agent, causing a simultaneous hydrolyzation and degradative oxidation, resulting in the formation of 6,9-difluoro-11,17-dihydroxy-16-methyl-17-carboxy-androsta-1,4-diene-3-one in high yield. Flumethasone 21-acetate is alternatively hydrolyzed to yield flumethasone free alcohol.