GB634741A - Preparation of compounds of the cyclopentanodimethylpolyhydrophenanthrene series - Google Patents

Abstract

D 17,20-3-Hydroxy-11-keto-21-acyloxypregnenes, of the general formula <FORM:0634741/IV (b)/1> (wherein Y represents an oxidation-resistant acyl group which can readily be removed by hydrolysis), are manufactured by the action of an acylating agent corresponding to the group Y, e.g. an anhydride of a monobasic or dibasic carboxylic acid, on D 17,20-3 : 21-dihydroxy-11-ketopregnene, which is made by reacting a D 17,20-3-acyloxy-11-keto-21-halopregnene with an alkali or alkaline-earth metal salt of an aliphatic carboxylic acid containing not more than six carbon atoms in the molecule (preferably in a solvent in which the metal salt has appreciable solubility), and saponifying the resulting 3 : 21-diacyloxy compound. In an example, D 17,20 - 3(a ) - acetoxy - 11 - keto - 21 - bromopregnene is refluxed with anhydrous potassium acetate in acetone, the resulting 3(a ) : 21-diacetoxy-compound is refluxed with methanolic potassium hydroxide, and the 3(a ) : 21-dihydroxy-compound so obtained is warmed with succinic anhydride in pyridine to produce D 17,20-3(a )-hydroxy-11-keto-21-hemisuccinoxypregnene. The product may be re-esterified in the 3-hydroxy group, e.g. by treatment with acetic anhydride. Alternative starting materials are the corresponding compound having the 3-acetoxy group in the cis-form, and compounds in which the 3-acetoxy group is replaced by a group derived from propionic, butyric, valeric, caproic, capric, benzoic, toluic or phenylacetic acid. Other alkali or alkaline-earth metal salts which may be used are those of propionic or butyric acid, whilst additional acid anhydrides specified for the esterification of the 21-hydroxy group are acetic and phthalic anhydrides. Specification 630,431 is referred to. The Specification as open to inspection under Sect. 91 comprises also the use as starting materials of D 17,20-3-hydroxy-11-keto-21-halopregnenes instead of the 3-acyloxy compounds, and the use of acids instead of anhydrides in the esterification step. This subject-matter does not appear in the Specification as accepted.