GB1203637A - New piperidine derivatives the preparation and compositions containing same - Google Patents

Abstract

1,203,637. Alkyl esters of 4-(prop-2-ynyl)- piperidine-4-carboxylic acids. J. R. GEIGY A.G. 12 July, 1967 [13 July, 1966], No. 32062/67. 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 4 carbon atoms in the alkyl radical, a 2-(N-alkanoylanilino) ethyl group having not more than 4 carbon atoms in the alkanoyl radical, a 2-anilinoethyl, 2-(N-allylanilino)ethyl, a 2-phenoxyethyl, a 2-benzoylethyl or a cinnamyl group 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-yn-l-ol and an inorganic or an organic acid, (b) by subjecting a 1-substituted-4-(prop-2-ynyl)-4-cyanopiperidine to alcoholysis in one of the usual ways, (c) by reacting a 4-alkoxycarbonyl-4- (prop-2-ynyl)piperidine with a reactive ester of an alcohol of the formula R 1 OH and an inorganic or an organic acid or (d) by converting a 1 - substituted - 4 - (prop - 2 - ynyl)piperidine- 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 HaI, 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 -alkozyearbonylpiperidine. 1 - Substituted - 4 - cyano - 4 - (prop - 2 - ynyl)- piperidines 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-carbox amide and dehydrating the latter with thionyl chloride to give a 1-substituted-4-cyanopiperidene which is then reacted with a reactive ester of prop-2-yn-l-ol and an inorganic or an organic acid. 1 - Substituted - 4 - (prop - 2 - ynyl)piperidine- 4-carboxylic acids are prepared by hydrolysing the corresponding nitriles and the acids are converted into 1 - substituted - 4 - prop - 2 - ynyl)- piperidine-4-carbonyl chlorides with thionyl chloride. 4 - (2 - Propynyl) - isonipecotinic acid C 1-4 alkyl ester is prepared by forming the lithium derivative of 1 - benzyloxycarbonyl - isonipecotinic acid C 1-4 alkyl ester (this alkyl ester is obtainable from isonipecotinic acid ethyl ester and chloroformic acid ethyl ester), treating the lithium-derivative with propargyl bromide and treating the resulting 1-benzyloxycarbonyl-4-(2- propynyl)isonipecotinic acid ethyl ester with HBr. 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.