GB1086952A - Antifibrinolytically active isomer of 4-aminomethyl-cyclohexane carboxylic acid - Google Patents

Abstract

The invention comprises a 4-aminomethylcyclohexanecarboxylic acid isomer in substantially pure state assaying at least about 90% antifibrinolytically active material (and defined also by its electrophoresis characteristics), and the preparation thereof by the following processes: (1) synthesis from the appropriate isomer of a cyclohexane compound having in the 4-position an aminomethyl group or a substituent and in the 1-position a carboxylic acid group or a substituent convertible thereto (but excluding 4 - aminomethylcyclohexanecarboxylic acid itself), by converting the former and/or the latter substituent(s) to the desired final substituent(s); (2) isomerization of the inactive isomer by heating it, alone or in admixture with active isomer, in a compatible liquid vehicle in which an alkali metal carboxylate of the active isomer is soluble, together with a sufficient amount of an alkali metal alcoholate derived from a C1- 24 alkanol, benzyl alcohol or furfuryl alcohol, or an alkali metal hydride, hydroxide or amide, for a time sufficient to form the alkali metal salt of the active isomer, separating this and converting it to the free acid by passing a solution thereof in an aqueous solvent through a bed of a cation exchange substance. Examples given for process (1) are: (a) dimethyl cyclohexane-1,4-dicarboxylate --> mono-ester --> mono-ester acid halide --> mono-ester amide methyl 4-cyanocyclohexanecarboxylate --> 4-cyanocyclohexanecarboxylic acid --> 4-aminomethylcyclohexanecarboxylic acid; (b) 4-aminomethylcyclohexanemethanol --> 4 - benzoylaminomethylcyclohexanemethanol --> 4-benzoylaminocyclohexanecarboxylic acid --> aminomethylcyclohexanecarboxylic acid. If either of these processes is carried out with the other isomer of the starting material, it yields a suitable starting material for process (2), in which alternatively there may advantageously be used the isomeric mixture obtained by catalytic hydrogenation of a benzoic acid having in the 4-position an aminomethyl group or a substituent convertible thereto. Pharmaceutical preparations (e.g. tablets, capsules, elixirs and injection solutions) comprise the isomer of the invention in association with at least one pharmaceutically acceptable carrier.