Patent GB-517277-A (GB)
Title: Manufacture of ketones of the cyclopentanopolyhydrophenanthrene series
IPC: C07J1/00
Filed: 1938-07-14
Abstract: 517,277. Cyclopentanopolyhydrophenanthrene ketones. SOC. OF CHEMICAL INDUSTRY IN BASLE. July 14, 1938, Nos. 20901 and 20902. Convention dates, July 14, 1937, and June 9, 1938. [Class 2 (iii)] Cyclopentanopolyhydrophenanthrene ketones are prepared by reacting with an organic metal compound a compound of this series containing a carboxylic acid group or a derivative of such a group connected to the nucleus in the 17- position directly or through one or more carbon atoms and containing in the nucleus a keto group or an enol derivative thereof. Derivatives of the carboxylic group which are specified include carboxylic acid amide groups, nitrile groups, carboxylic acid halide, anhydride, ester or salt groups. Parent materials mentioned include saturated and unsaturated halides, nitriles, amides, substituted amides, anhydrides or esters of 3-keto-aetio-cholanic acids, 3-keto-17-oxy-aetiocholanic acids, 3:11- diketoaetiocholanic acids, 3-keto-11-oxy-aetiocholanic acids, 3-keto-11-oxy-17-oxy-aetiocholanic acids, and also corresponding compounds of bisnorcholanic acid, cholane-17-acetic-acid, or norcholanic acid. Derivatives of these acids may be used such as esters, ethers, enol esters and enol ethers. The organic metal compounds which may be used comprise saturated or unsaturated compounds of metals with substituted or unsubstituted hydrocarbon residues. The substitutes may be any monovalent residue containing carbon such as one or more alkyl, cycloalkyl, aralkyl, aryl, cyanogen or substituted carboxyl groups. Compounds mentioned include metal hydrocarbon compounds such as dialkyls of zinc magnesium or mercury, organic metal halides such as those of mercury, magnesium or zinc and in particular the methyl-, ethyl-, allyl-, vinyl-, acetylene-, methylethyl-, cyclohexyl-, phenyl or benzoylmagnesium or -zinc-halides. Instead of using the already prepared organic metal compound the individual components of the compound may be used. This is particularly necessary when the organic metal compound is difficultly accessible of compounds from chloromethyl ether and vinyl bromide. When organomagnesium halides are employed it is desirable to protect the keto group by transformation into its enol derivative. The reaction products are worked up by decomposition with a dilute acid. In an example, the 3-enol acetate of #<4À><5>-3 keto aetio cholenic acid is converted into the corresponding acid chloride by treatment with thionyl chloride and then reacted with zinc dimethyl in toluene solution. The reaction product is worked up by treatment with dilute hydrochloric acid and extraction with ether to give the 3-enol acetate of #<4À><5>-pregnene-3:20 dione. This is saponified with sodium carbonate to progesterone. Instead of zinc dimethyl there may be used methyl zinc iodide. If ethyl zinc iodide or dipropyl zinc are used, the final product comprises homologues of progesterone. Specification 491,798 is referred to. The Specification as open to inspection under Sect. 91 comprises also the use as parent materials of compounds of the cyclopentanopolyhydrophenanthrene series which do not contain a keto group in the nucleus. In addition, compounds of the oestrane and hydro-oestrane series are referred to. The carboxylic acid group may moreover be attached at any point on the nucleus. The specification as open included also the subject-matter which now forms the subject matter of Specification 517,307. Many additional organic metal compounds and one extra example were also included. This subject-matter does not appear in the Specification as accepted.