GB765854A - Improvements in or relating to substituted piperidines - Google Patents

Abstract

The invention comprises: (a) carbinols of the general formula: <FORM:0765854/IV(b)/1> wherein Q is phenyl, Q1 is phenyl or pyridyl, one of R and R1 is hydrogen and the other a hydroxy group, and R2 is hydrogen or an alkyl group of 1-6 carbon atoms, and salts of certain of these compounds; (b) the preparation of the compounds in which R is a hydroxy group and R1 is hydrogen by reacting a ketone QCOQ1 with a methylpyridine to form a carbinol, reducing this to a pipecolyl carbinol, and, if desired, subjecting the latter to reductive alkylation; (c) the preparation of the compounds in which Q1 is pyridyl, R is hydrogen, R1 is a hydroxy group and R2 is methyl by reacting a lithium substituted benzylpyridine with a 1-methylpiperidine aldehyde; (d) conversion of the products of (b) and (c) to acid addition and quaternary ammonium salts. In examples: (1) benzophenone is reacted with 4-picoline in the presence of sodamide and the resulting diphenyl 4-picolyl carbinol is hydrogenated in acetic acid in the presence of platinum to produce diphenyl 4-pipecolyl carbinol, the hydrochloride of which is described; (3) 3-picoline similarly yields diphenyl 3-pipecolyl carbinol; (3) 2-picoline similarly yields diphenyl 2-pipecolyl carbinol; (4) the product of (3) is refluxed with formalin and formic acid to form diphenyl 1 - methyl - 2 - pipecolyl carbinol, the oxalate of which is described; (5) the product of (4) is quaternated with methyl bromide in ether; (6) lithium is reacted with bromobenzene in ether and the product with 2-benzylpyridine, and the resulting solution is stirred with an ethereal solution of 1 - methyl - 4 - piperidine aldehyde to produce a - (2 - pyridyl) - benzyl 1 - methyl-4 - piperidyl carbinol; (7) the product of (1) is shaken with formalin in methanol, after which Raney nickel is added and the mixture hydrogenated under pressure to give dimethyl 1-methyl-4-pipecolyl carbinol. The products are useful as antispasmodic agents, especially in the form of their acid addition and quaternary ammonium salts (e.g. sulphates, phosphates, hydrochlorides, levulinates, mucates, acetates, tartrates, methobromides and methiodides), and as intermediates in the process of Specification 765,853.ALSO:Therapeutic preparations for the relief of smooth-muscle spasms contain carbinols of the general formula:- <FORM:0765854/VI/1> (wherein Q is phenyl, Q1 is phenyl or pyridyl, one of R and R1 is hydrogen and the other a hydroxy group, and R2 is hydrogen or an alkyl group of 1-6 carbon atoms) or an acid addition or quaternary ammonium salt thereof. These compounds may be employed in the form of an aqueous solution of a water-soluble salt (e.g. of sulphuric, phosphoric, hydrochloric, leonlinic, mucic, acetic or tartaric acid) or incorporated in a tablet or capsule base. The free bases or their sparingly soluble salts may be administered when a slow and prolonged effect is desired.