GB563889A - Steroidal hormone intermediates and their preparations - Google Patents

Abstract

Androstane compounds are prepared from D 16-20-keto pregnane compounds having no nuclear keto substituents by treatment with an oxime forming reagent followed by subjecting the product to the Beckmann transformation, and hydrolysing the product. The oxime forming reagent may be either hydroxylamine or an acid addition product thereof, preferably the sulphate. A dehydrohalogenating agent, such as sodium acetate or pyridine, may be present. The Beckmann rearrangement may be carried out with any agent known to be suitable for this purpose, such as acidic agents, and agents which are reactive with water to form strong acids. Agents mentioned include hydrochloric and sulphuric acids, phosphorus pentachloride, thionyl chloride, antimony pentachloride, benzene sulphonyl chloride, benzoyl chloride, benzene sulphonyl bromide, methane sulphonyl chloride, anthraquinone sulphonyl chloride, and p-nitrobenzene sulphonyl chloride. The presence of a diluent such as acetic acid dioxane, ether, benzene pyridine dimethylaniline, tributylamine, N-ethylmorpholine or quinoline is usually desirable, the preferred solvent being a tertiary amine. Starting materials mentioned include D 4,16 - pregnadienone - 20, D 5,6 - pregnadienone - 20, D 5,16 - pregnadienol - 3 (b ) - one - 20 - acetate, 3 - chloro - D 5,16-pregnadienone-20, D 16-allo-pregnenediol-3(b ) : 6 - one - 20 - diacetate, D 4,16 - pregnenediol-3 : 6-one-20-diacetate, D 5,6-pregnenediol-3 : 4-one - 20 - dibenzoate. In examples: (1) D 16-pregnenol - 3 - (b ) - one - 20 acetate in alcoholic solution is treated with an aqueous solution of hydroxylamine hydrochloride and sodium acetate at room temperature to give D 16-pregnenol-3(b )-one-20-acetate oxime, which is treated with p-toluene sulphonyl chloride in pyridine solution, and then hydrolysed with 10 per cent aqueous sulphuric acid to form etio-cholanol-3(b )-one-17-acetate. (2) D 5,16-pregnadienol-3(b )-one-20-acetate in alcohol is treated with an aqueous solution of sodium acetate and hydroxylamine as in example 1 to form D 5,16-pregnadienol-3(b )-one-20-acetate oxime which is p treated with p-toluenesulphonyl chloride in pyridine solution and then hydrolysed as before to give D 5-etio-cholenol-3(b )-one-17-acetate. (3) D 5,16-pregnadienol-3(b )-one-20-acetate is allowed to stand four days in pyridine solution with hydroxylamine hydrochloride when benzenesulphonyl chloride is added and then hydrolysed as before to D 5-etio-cholenol - 3(b ) - one - 17 - acetate. (4) D 5,16-pregnadienol - 3(b ) - one - 20 - acetate oxime is treated with phosphorus pentachloride in dioxane solution, and then hydrolysed with dilute hydrochloric acid to give dehydroisoandrosterone. Specification 552,047 is referred to.