Patent GB-715883-A (GB)
Title: Improvements in or relating to cyclopentanopolyhydrophenanthrene compounds and methods of production thereof
IPC: C07J75/00
Filed: 1950-12-19
Abstract: The invention comprises (i) D 1,4,6-3-ketosteroids, especially those of the general formula <FORM:0715883/IV (b)/1> (wherein A represents C = O or CH - OR and R represents hydrogen or the residue of a fatty acid of not more than six carbon atoms or of an aromatic acid); (ii) the preparation thereof by (a) treating a D 4-3-ketosteroid with two molecular proportions of bromine at a low temperature in the presence of a fatty acid containing not more than six carbon atoms in the molecule (preferably at 0-15 DEG  C. in the presence of ether and glacial acetic acid) or with two molecular proportions of N-bromosuccinimide in the presence of strong light, or treating a 2- or 6-bromo- D 4-3-ketosteroid with half the quantity of the said brominating agents, and thereafter in each case dehydrobrominating the resulting dibromo-D 4-3-ketosteroid, or (b) treating a D 1,4-3-ketosteroid with one molecular proportion of N-bromosuccinimide in the presence of a bromination catalyst and dehydrobrominating the resulting 6-bromo- D 1,4-3-ketosteroid; (iii) the production of equilenin derivatives of the general formula <FORM:0715883/IV (b)/2> (wherein R1 represents hydrogen or an acyl residue as defined for R) by preparing a compound of the general formula given at (i) by the process of (ii) (a), heating it to 500-650 DEG  C. in the presence of a hydrogen donor solvent, acylating the resulting D 6-dehydroestrogen, and dehydrogenating the product in the presence of a dehydrogenation catalyst or dehydrogenating agent, followed, if desired, by saponification. In examples (1) testosterone acetate is treated with bromine in acetic acid and ether in the presence of hydrogen bromide at 0 DEG  C. to produce a dibromo derivative; (2) D 4 androstene - 3 : 17 - dione is similarly dibrominated; (3) and (4) 2- and 6-bromo- D 4-androstene-3 : 17-dione are brominated as in (1) but with half the quantity of bromine; (5) 6-bromotestosterone acetate is brominated as in (3); (6) testosterone acetate is dibrominated with N-bromosuccinimide in carbon tetrachloride while exposed to strong light; (7) and (8) 2- and 6-bromotestosterone acetate are brominated as in (6), but using less N-bromosuccinimide; (9) the product of (1) or (5)-(8) is refluxed with collidine to form D 1,4,6-17-acetoxyandrostatrien-3-one; (10) the product of (9) is saponified to the 17-hydroxy compound; (11) the product of (2), (3) or (4) is treated as in (9) to give D 1,4,6-androstatriene-3 : 17-dione; (12) the same product is obtained by treating D 1,4-androstadiene-3 : 17-dione with N-bromosuccinimide in carbon tetrachloride in the presence of benzoyl peroxide and refluxing the resulting 6-bromo compound with collidine; (13) the product of (9) is similarly prepared from D 1,4-17-acetoxyandrostadiene-3-one; (14) the product of (11) is heated with mineral oil at 600 DEG  C. to produce D 6-dehydroestrone; (15) the product of (14) is esterified by heating with acetic anhydride and pyridine; (16) the product of (15) is reduced with lithium aluminium hydride to D 6-dehydroestradiol; (17) the product of (9) is treated as in (14) to form D 6-dehydroestradiol 17-monoacetate, which is further esterified with acetic anhydride and pyridine to the 3 : 17-diacetate, or saponified to the product of (16); (18) the product of (15) is refluxed with selenium dioxide in glacial acetic acid to give equilenin acetate, which is saponified to equilenin; (19) the diacetate of (17) similarly yields 17-dihydroequilenin-17b  3 : 17-diacetate and 17-dihydroequilenin-17b .  Specification 715,940 is referred to.