GB941748A - Derivatives of 3-methyl-4-alkoxycarbonyl-4-phenylpiperidine - Google Patents

Abstract

The invention comprises compounds of the general formula: <FORM:0941748/C2/1> and pharmaceutically useful non-toxic salts thereof wherein R is a C1-3 alkyl group L is a C1-7 alkyl group, the b -(b -hydroxyethoxy)-ethyl, cinnamyl, 3-hydroxy-3-phenylpropyl or b -benzoylethyl group. The compounds may be prepared by condensation of a halide L-X, where X is a halogen atom, with 3-methyl-4-alkoxycarbonyl-4-phenylpiperidine or methylation with formaldehyde and formic acid (when L is methyl). The secondary alcohols may be prepared by reducing the corresponding ketone and the compound wherein L is a b -benzoylethyl group by heating acetophenone with paraformaldehyde and a 3-methyl-4-alkoxycarbonyl-4-phenylpiperidine hydrochloride. Quaternary ammonium salts are prepared by reacting the bases with esters such as alkyl, alkenyl, aralkyl halides and toluene sulphonates or alkylene-halohydrins. The compound of the invention comprise both cis and trans-isomers depending on the relative positions of the 3-methyl and 4-ester groups, the isomers being termed 3a - and 3b -methyl compounds respectively. 3-Methyl-4-alkoxycarbonyl-4-phenylpiperidines are prepared by reacting N-(b -hydroxyethyl)-N-(b -hydroxypropyl)amine with 4-toluenesulphonyl chloride to give N-(b -hydroxyethyl)-N-(b -hydroxy-propyl) -4-toluenesulphonamide converting this to N-(b -chloroethyl)-N-(b -chloropropyl)-4-toluenesulphonamide with thionyl chloride, reacting this with phenylacetonitrile to give 1-(4-toluenesulphonyl)-3-methyl-4-phenyl-4-cyanopiperidine, separating this into the 3a and 3b isomers by extraction with methanol hydrolysing the cyano group to give 1-4-toluene-sulphonyl)-3-methyl-4-phenyl-4-carboxypiperidine committing this to an alkyl ester and removing the sulphonyl group by treatment with phenol and hydrogen bromide.