GB743921A - Dehydrohalogenation of -a-halo-keto steroids - Google Patents

Abstract

Keto-steroids having a double bond between carbon atoms vicinal to a nuclear keto group are prepared by reacting a keto-steroid, which possesses a chlorine or bromine atom on the carbon atom alpha to the keto group and a hydrogen atom on the next adjacent carbon, with a halide of boron, silicon or a metal having an ionic radius of 0.20 to 0.80 inclusive, in a basic organic solvent, preferably in the presence of a strong acid catalyst, e.g. sulphuric acid, p-toluene sulphonic acid or a - or b -naphthylsulphonic acid. Specified metal halides are those of lithium, beryllium, magnesium, aluminium, zinc and titanium. The solvents are "lewis" bases, preferably of high dielectric constant, e.g. N:N-dialkylamides, tertiary amines and their N-acyl derivatives (many examples listed), and an auxiliary solvent, e.g. benzene, toluene or butanol, may be present. In examples (1) 4-bromo-17a -hydroxy-21-acetoxypregnane-3:11:20-trione is heated with lithium chloride in dimethylformamide under nitrogen and the product treated with water to give cortisone acetate. Repetition using lithium bromide, lithium iodide, magnesium or berylium chloride in N:N-dimethylacetamide, pyridine or N-formylpiperidine, or using the corresponding 4-chloro-steroid gives the same product. Other cortisone esters are similarly prepared. (2) 17a - hydroxy - 21 - acetoxyallopregnane - 3,11,20 - trione is dibrominated and treated as in (1) to yield cortisone acetate. (3) D 1 - cholestenone is prepared from 2-bromocholestanone using lithium chloride in collidine. (4) D 5-7-ketocholenic acid from 6-bromo-7-ketocholanic acid using titanium tetrachloride in N:N-dimethylpropionamide. (5) D 9(11)-3a -acetoxy - 12 - ketocholenic acid from 3a - acetoxy - 11 - bromo - 12 - ketocholanic acid using magnesium bromide in morpholine. 11-Ketoprogesterone and progesterone are similarly obtained as in (1) from brominated pregnane-3,11,20-trione and 3,20-dione respectively. 4 - Chloro - 17 - a - hydroxy - 21 - acetoxypregnane - 3,11,20 - trione is prepared from 3a , 17a -dihydroxy - 21 - acetoxypregnane - 11,20 - dione by treatment with N-chlorosuccinimide. Specification 710,557 is referred to.