GB788306A - Improvements in or relating to the preparation of steroid compounds - Google Patents

Abstract

D 1 : 4-3-Ketosteroids are prepared by heating a 2 : 4 - dibromo - 3 - keto - 5a - steroid with semicarbazide or a salt thereof in, as reaction medium, a substituted amide of formula R1.CO.NR11R111 (R1 is a hydrogen atom or a aliphatic group containing from 1 to 6 carbon atoms, R11 and R111 are each an alkyl group having from 1 to 4 carbon atoms or together form part of a heterocyclic ring), and decomposing the resulting semi-carbazone, e.g. by heating in an aqueous mixture of acetic and pyruvic acids. Preferred starting materials are of the formula: <FORM:0788306/IV (b)/1> in which R1 is a ketonic oxygen atom or a hydroxyl group, R2 is a hydrogen or halogen atom, R3 is an acyl group and R4 is hydrogen or an acyl group. Specified amides are N : N-dimethyl acetamide, N : N-dimethyl formamide, N : N-dimethyl valeramide, N : N-diethyl formamide, N : N-dipropyl formamide, N : N-dibutyl formamide, N-formylpiperidine and N-formylmorpholine, and the reaction is normally carried out at between 50 DEG and 180 DEG C., preferably between 80 DEG and 100 DEG C.; a small quantity of water, up to 10 per cent, is preferably present in the medium. In examples: (1) to (3) 2 : 4 - dibromo - 4 : 5a - dihydrocortisone 21-acetate and semicarbazide or its hydrochloride are heated in aqueous dimethyl formamide, or aqueous or anhydrous dimethyl acetamide, the solvent evaporated and, after treatment with pyruvic and glacial acetic acids, crude 1 : 2-dehydrocortisone acetate is extracted with methylene chloride and if necessary re-acetylated with acetic anhydride-pyridine; (4) 2 : 4-dibromo-4 : 5a -dihydrocortisone 17 : 21-diacetate similarly yields crude 1 : 2-dehydrocortisone 17 : 21-diacetate.