Preparation of flumethasone and its 17-carboxyandrostene analog

摘要

A process for the preparation of high purity flumethasone in high yield involves C3 protecting 9,11beta-epoxy-17alpha,21-dihydroxy-16alpha-methylpregna-1,4-diene-3,20-dione,21-acetate, fluorinating at 6alpha, 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 6alpha,9alpha-difluoro-11beta,17alpha-dihydroxy-16alpha-methyl-17beta-carboxy-androsta-1,4-diene-3-one in high yield. Flumethasone 21-acetate is alternatively hydrolyzed to yield flumethasone free alcohol.