Patent GB-797448-A (GB)
Title: Novel piperidine compounds and their production
Inventor: FREARSON PETER MARSHALL
Filed: 1955-11-28
Abstract: The invention comprises norpethidines of the general formula: <FORM:0797448/IV (b)/1> in which X is a substituted or unsubstituted alkoxy, aralkoxy, aryloxy or cycloalkyloxy group or a heterocyclic residue containing an oxygen atom, and R is a straight or branched chain alkylene group which contains from one to six carbon atoms (preferred compounds being those in which R is -CH2.CH2- and X is ethoxy, isopropoxy, phenoxy or benzyloxy), and their manufacture by reacting norpethidine with a compound X-R-Hal in which Hal is a chlorine, bromine or iodine atom, or by reacting a di (chloroethyl)amine substituted by the group X-R with benzyl cyanide and hydrolysing and esterifying the resulting 4-phenyl-4-cyanopiperidine, or, when X is a substituted or unsubstituted alkoxy, aralkoxy, aryloxy or cycloalkyloxy group, by reacting a 1-(halogenoalkyl) norpethidine of the general formula: <FORM:0797448/IV (b)/2> with a compound X-Na.  Examples describe the preparation of 1 - (21 - ethoxyethyl norpethidine, 1 - (21 - 411 - tetrahydropyranylethyl)norpethidine, 1 - (31 - ethoxypropyl) norpethidine hydrobromide, 1 - (41 - ethoxybutyl)norpethidine and its methiodide, 1 - (51-ethoxyamyl)norpethidine, 1 - (21 - 211 - ethoxy-ethoxyethyl)norpethidine, 1 - (21 - methoxyethyl)norpethidine, 1 - (21 - propoxyethyl) norpethidine, 1 - (21 - isopropoxyethyl)norpethidine, 1 - (21 - n - butoxyethyl)norpethidine, 1-(21 - cyclohexyloxyethyl)norpethidine hydrobromide, 1 - (21 - benzyloxyethyl)norpethidine and its hydrobromide, 1-(21-phenoxyethyl) norpethidine and its hydrobromide, 1-(21-p-chlorophenoxyethyl)norpethidine hydrobromide, 1 - (21 - m - chlorophenoxyethyl)norpethidine hydrobromide, 1 - (21 - p - methoxyphenoxyethyl)norpethidine hydrobromide, 1 - (21-m - methoxyphenoxyethyl)norpethidine hydrobromide, 1 - (21 - p - acetamidophenoxyethyl) norpethidine hydrobromide, 1 - (21 - p - aminophenoxyethyl)norpethidine and its dihydrochloride and dihydrobromide, 1 - (21 - p - carbethoxyphenoxyethyl)norpethidine hydrobromide, 1 - (21 - tetrahydrofurfuryloxyethyl) norpethidine, 1 - (21 - a  - tetrahydropyranyl methoxy)ethylnorpethidine, 1 - (21 - phenoxyethyl)norpethidine hydrobromide, 1 - (21 - p-nitrophenoxyethyl)norpethidine hydrobromide, 1 - (21 - p - aminophenoxyethyl)norpethidine dihydrochloride, 1 - (21 - m - methylphenoxyethyl)norpethidine hydrobromide, 1 - (21 - o-methylphenoxyethyl)norpethidine hydrobromide and 1 - (21 - ethoxypropyl)norpethidine.  The following are obtained as intermediates: 1 - (21 - chloroethyl)norpethidine (from the corresponding hydrochloride), 4 - (21 - chloroethyl) tetrahydropyran (by the action of thionyl chloride on 4-(21-hydroxyethyl) tetrahydropyran), di - (2 - chloroethyl) - 21 - phenoxyethylamine (by reacting 2-chloroethyl phenyl ether with diethanolamine and treating the product with thionyl chloride), and 4-carboxy-1-(21-phenoxyethyl) - 4 - phenyl - piperidine (by condensing di - (2 - chloroethyl) - 21 - phenoxyethylamine with benzyl cyanide and hydrolysing the 4-cyano - 1 - (21 - phenoxyethyl) - 4 - phenylpiperidine so formed. Specification 762,689 is referred to.