Patent GB-942663-A (GB)
Title: Phenyl cyclohexane and -cyclohexene derivatives, new intermediates for the synthesis of the female sex hormone estrone and other steroids
IPC: C07D261/20
Filed: 1960-04-06
Abstract: The invention comprises compounds of the general formula shown in Fig. 1 wherein R is H or CH3, R1 is CN, COOCH3 or COOC2 H5 and R2 is H, CH3 or C2H5 and also wherein RR1 is =H2 or =CHOH and R2, has the above significance; compounds of the formula shewn in Fig. II wherein R is H or CH3 and R1 is CH3 or C2H5 and the position 11 21 is unsaturated; compounds of th formula shown in Fig. IV wherein R is H or CH3; and compounds of the formula shown in Figs. VI, VII, VIII, IX, X, XI, XII, XIII, XIV and XVIII. The invention also comprises methods of preparing (a) a compound of the formula shown in Fig. III by cyclisation of a compound of the formula shown in Fig. XIV wherein R is H, R1 and R2 are selected fro methyl and ethyl by treatment with aqueous alkali; (b) a compound of the formula shown in Fig. XIV by condensing a compound of the formula shown in Fig. XV with a compound of the formula shown in Fig. XVI in the presence of alkoxides selected from sodium and potassium alkoxides and dimethyl sulphate (c) a compound of the formula shown in Fig. III by cyclisation of a compound of the general formula shown in Fig. XIV, wherein R is H, and R1 and R2 are selected from methyl and ethyl cyclisation being carried out by treating the compounds shown in Fig. XIV with alcoholic alkali whereby ketonic fission of the b -keto ester group results in elimination of -COOR, and there occurs saponification o -COOR2 to COOH and the usual aldol condensation occurs followed by elimination of water; (d) a compound of the general formula shown in Fig. II where R=H or CH3 and R1=CH3 or C2H5 by treating a compound of the general formula shown in Fig. XIV wherein R is H or CH3 and R1 and R2 are CH3 or C2H5 with sodium alkoxide whereby cyclisation and saponification occurs; (e) a compound of the formula shown in Fig. IV where R is H by reduction of the compound shewn in Fig. IV with lithium and anhydrous liquid ammonia; (f) a method of preparing a compound of the formul shown in Fig. IV where R is methyl by esterification of a compound of the formula shown in Fig IV where R is H with diazo methane or methanol/sulphuric acid; (g) a compound of the formula shown in Fig. IV where R is H by hydrogenation of the compound shown in Fig. V in the presence o palladium on charcoal catalyst followed by treatment with aqueous or alcoholic alkali; (h) a compound of the formula shown in Fig. VI by formylation of a compound of the formula shown in Fig. with ethyl or methyl formate in the presence of dry sodium alkoxide or potassium alkoxide in dr ether, benzene or petroleum ether; (i) a compound of the formula shown in Fig. VII by a similar process from a compound of the formula shown in Fig. IV; (j) a compound of the formula shown in Fig. XIII by treating a compound of the formula shown in Fig. VI with hydroxyamine hydrochloride in the presence of acetic acid; (k) a compound of the formula shown in Fig. XII by a similar process fro a compound of the formula shown in Fig. VII; (l) a compound of the formula shown in Fig. VII by treating a compound of the formula shown in Fig. XIII with sodium alkoxide or potassium alkoxide and a methyl halide; (m) a compound of the formula shown in Fig. IX by a similar process from a compound of the formula shown in Fig. XII; (n) a compound of the formula shown in Fig. X b treating a compound of the formula shown in Fig VIII with potassium carbonate in aqueous methanol; (o) a compound of the formula shown in Fig. XI by a similar process from a compound of the formula shown in Fig. IX; (p) a compound of the formula shown in Fig. XVII by reduction of a compound of the formula shown in Fig. X with lithium and anhydrous liquid ammonia followed by treatment with methanolic hydrogen chloride; (q) a compound of the formula shown in Fig. XVII by treatment of a compound of the formula shown in Fig. XI with methanolic hydrogen chloride; (r) a compound of the formula shown in Fig. XVIII by esterification of a compound of the formula shown in Fig. II in which R is H, R1 is C2H5 with diazomethane followed by methylation with sodium, sodium alkoxide or potassium alkoxide or sodium hydride and a methyl halide; (s) a compound of the formula shown in Fig. XVIII by esterification of a compound of the formula shown in Fig. II where R is CH3 and R1 is C2H5; (t) a compound of the formula shown in Fig. XVII comprising treating dimethyl, diethyl or ethyl methyl b -keto-adipate with b -dimethylamino-p-methoxypropiophenone hydrochloride to form a compound of the general formula shown in Fig. XIV wherein R is H and R1 and R2 are methyl or ethyl radicals, cyclising to form a compound of the formula shown in Fig. III by treatment with aqueous alkali, esterifying to form the methyl ester, formylating with methyl or ethyl formate in the presence of sodium- or potassium alkoxide to form a compound of the formula shown in Fig. VI, treating the latter with hydroxylamine hydrochloride in acetic acid to form a compound of the formula shown in Fig. XIII treating the latter with alkali alkoxide and a methyl halide to form a compound of the formula shown in Fig. VIII which is partially hydrolysed by treatment with potassium carbonate in aqueous methanol to produce a compound of the formula shown in Fig. X, reducing the latter compound with lithium and anhydrous ammonia followed by treatment with methanolic hydrogen chloride, and (u) a compound of the formula shown in Fig. XI by the reductio of the compound of the formula shown in Fig. X by lithium and anhydrous ammonia. Examples are furnished. Specification 942,664 is referred to.  <FORM:0942663/C2/1>