GB1205041A - New piperidine derivatives their preparation and compositions containing same - Google Patents

Abstract

1,205,041. Alkyl esters of 4-allylpiperidine-4- carboxylic acids. J. R. GEIGY A.G. 12 July, 1967 [13 July, 1966], No. 32061/67. Heading C2C. Novel compounds of the formula and their acid addition salts, where R 1 is a C 7-9 alkyl group, a phenylalkyl group having not more than four carbon atoms in the alkyl radical, a 2-(N-alkanoylanilino)-ethyl group having not more than four carbon atoms in the alkanoyl radical, a 2-anilinoethyl, a 2-(N-allylanilino)- ethyl, a 2-phenoxyethyl, a 2-benzoylethyl or a cinnamyl radical and R 2 is a C 1-4 alkyl group are prepared (a) by reacting the alkyl metal derivative of a 1-substituted-4-alkoxycarbonylpiperidine with a reactive ester of prop-2-en-1-ol and an inorganic or an organic acid, (b) by the partial hydrogenation of a 1-substituted-4-alkoxycarbonyl - 4 - prop - 2 - ynylpiperidine in the presence of a suitable catalyst, e.g. Lindlar catalyst, (c) by subjecting a 1-substituted-4- allyl-4-cyanopiperidine to alcoholysis in one of the usual ways, (d) by reacting a 4-alkoxycarbonyl-4-allylpiperidine with a reactive ester of an alcohol of the R 1 OH and an inorganic or an organic acid or (e) by converting a 1-substituted - 4 - allylpiperidine - 4 - carboxylic acid into a C 1-4 alkyl ester by one of the usual methods (e.g. via the acid chloride). 1 - Substituted - 4 - alkoxycarbonylpiperidines are prepared by reacting 4-alkoxycarbonylpiperidines with a halo-compound of the formula R 1 Hal, where Hal is chlorine, bromine or iodine to form a 1-substituted-4-alkoxycarbonylpiperidinium halide which is then hydrogenated in the presence of rhodium on alumina to give a 1-substituted-4-alkoxycarbonylpiperidine. 1 - Substituted - 4 alkoxycarbonyl - 4 - prop - 2<SP>1</SP>-ynylpiperidines are prepared by reacting a 1 - substituted - 4 - alkoxycarbonylpiperidine with a reactive ester of prop-2-yn-1-ol with an inorganic or an organic acid. 1 - Substituted - 4 - allyl - 4 - cyanopiperidines are prepared by reacting piperidine-4-carboxamide with a reactive ester of the alcohol R 1 OH and an inorganic or an organic acid to give a 1 - substituted - piperidine - 4 - carboxamide and dehydrating the latter with thionyl chloride to give a 1-substituted-4-cyanopiperidine and then introducing the allyl radical as in (a) above. 4 - Alkoxycarbonyl - 4 - allylpiperidines are prepared by reacting a 4-alkoxycarbonylpiperidine with benzyl chloroformate to give a 4-alkoxycarbonyl - 1 - benzyloxycarbonylpiperidine, the alkali metal derivative of which reacts with a reactive ester of allyl alcohol and an inorganic or an organic acid to give a 4-alkoxycarbonyl-4- allyl - 1 - benzyloxycarbonylpiperidine which reacts with hydrogen bromide in glacial acetic acid to give a 4-alkoxycarbonyl-4-allylpiperidine. 1 - Substituted - 4 - allylpiperidine - 4 - carboxylic acids are prepared by hydrolysing the corresponding nitriles and the acids are converted into 1-substituted-4-allylpiperidine-4-carbonyl chlorides with thionyl chloride. Therapeutic compositions effective as analgesics and antitussives comprise at least one of the novel compounds of the above formula or an acceptable addition salt with an inorganic or an organic acid as the active component and can be administered as dragees, tablets, suppositories, lozenges, syrups and solutions for injection.