Patent GB-886961-A (GB)
Title: Steroid compounds and their preparation
IPC: C07J75/00
Filed: 1958-10-08
Abstract: The invention comprises compounds of the formulae <FORM:0886961/IV (b)/1> and <FORM:0886961/IV (b)/2> and the corresponding 3,17a ,21-triacetoxy, 3-methoxy, 3-methoxy-20-semicarbazono, and 3-methoxy-11b -hydroxy-compounds, compounds of the formulae <FORM:0886961/IV (b)/3> and <FORM:0886961/IV (b)/4> and 11b , 17a  - dihydroxy - 1 - methyl - 17b  - (1 - oxo - 2 - hydroxy - ethyl) - 4 - estren - 3 - one and -4,6-estradien-3-one and the corresponding 17b -(1-oxo-2-acyloxyethyl) compounds, and processes which comprise each stage and the whole of the following synthesis: 17a ,21-diacetoxy-1,4 pregnadiene-3,11,20-trione or the corresponding 1,4,6-pregnatriene is reacted with acetic anhydride in the presence of acetic acid and zinc chloride to form 3,17a -diacetoxy-1-methyl-17b -(1-oxo-2-acetoxyethyl)-1,3,5(10) -estratrien-11-one or the corresponding 1, 3, 5 (10), 6 - estratetraen - 11 - one, this compound is hydrolysed under extremely mild conditions, e.g. with sodium methylate in methanol, to form 3,17a -dihydroxy-1-methyl-17b - (1 - oxo - 2 - hydroxyethyl) - 1, 3, 5 (10) - estratrien-11-one or the corresponding 1,3,5(10),6-estratetraen compound, this compound is reacted with diazomethane to form 17a -hydroxy-3-methoxy - 1 - methyl - 17b  - (1 - oxo - 2 - hydroxy - ethyl)-1,3,5,(10)-estratrien-11-one or the corresponding 1,3,5(10),6-estratetraen, this compound is reacted with semicarbazide to form 17a -hydroxy - 3 - methoxy - 1 - methyl - 17b  - (1 - semicarbazono - 2 - hydroxyethyl) - 1, 3, 5 (10) - estratrien-11-one or the corresponding 1,3,5(10,6-estratetraen, this compound is reacted with sodium borohydride and the reaction products acidified to form 11b ,17a -dihydroxy-3-methoxy-1 - methyl - 17b  - (1 - oxo - 2 - hydroxyethyl) - 1,3,5,(10)-estratriene or the corresponding 1,3,5-(10),6-estratetraen, this compound is reacted with formalin to form 11b -hydroxy-3-methoxy-1-methyl - 17, 20, 20, 21 - bis (dioxymethylene) - 1,3,5(10)-estratriene or the corresponding 1,3,5-(10),6-estratetraene, this compound is reduced with lithium in ammonia and the product treated with formic acid to form 11b ,17a -dihydroxy-1-methyl - 17b  - (1 - oxo - 2 - hydroxyethyl) - 4 - estren-3-one or the corresponding 4,6-estradien, and this compound is acylated, e.g. with a lower alkanoic anhydride or benzoic anhydride, to form 11b , 17a -dihydroxy-1-methyl-17b -(1-oxo-2-acyloxyethyl-4-estren-3-one or the corresponding 4,6-estradien.  A number of detailed examples are given.  17a  21 - Diacetoxy - 1,4 - pregnadiene - 3, 11, 20-trione is prepared by treating 17a ,21-diacetoxy-4-bromo-pregnane-3,11,20-trione with bromine and hydrogen bromide in glacial acetic acid to form 17a ,-21 diacetoxy-2,4-dibromo-pregnane-3,-11,20-trione, and di-dehydrobrominating this compound with collidine.  17a , 21 - Diacetoxy - 1, ,4 6 - pregnatriene - 3,11,20-trione is prepared by refluxing 17a ,21-dihydroxy-4-pregnene-3,11,20-trione 21-acetate, isopropenyl acetate, benzene and p-toluene sulphonic acid, cooling and concentrating under reduced pressure in the presence of sodium acetate to form 3,17a ,21-triacetoxy-3,5-pregnadiene-11,20-dione, treating this compound with N-bromosuccinimide in dimethyl formamide to form 17a ,21-diacetoxy-6-bromo-4-pregnene-3,11, 20-trione, dehydrobrominating this compound with collidine to form 17a ,21-diacetoxy-4,6-pregnadiene-3,11,20-trione, refluxing this compound with isopropenyl acetate to form 3,17a ,21-triacetoxy-2;4,6-pregnatriene-11,20-dione, treating this compound with N-bromosuccinimide to form 17a , 21 - diacetoxy - 2 - bromo - 4, 6 pregnadiene - 3,11,20-trione, and dehydrobrominating this compound with collidine.