GB716700A - A new and improved analgesic and process for its production - Google Patents

Abstract

The invention comprises a ,a -diphenyl-a -ethoxyacetic acid - b 1 - dimethylaminoethyl ester of the formula <FORM:0716700/IV (b)/1> The compound is prepared by a process in which the hydroxyl group of benzilic acid or its functional derivatives is etherified with ethyl alcohol and its carboxyl group is esterified with dimethyl-aminoethanol, in either order. The etherification can be effected by transforming the hydroxy group with alkali metals or alkaline earth metals, their alcoholates or amides or with metal organic compounds into the corresponding alcoholates and then reacting these with halogen-substituted etherification components. Alternatively benzilic acid is treated with thionyl chloride or bromide and the resulting diphenyl halogenacetic acid or its carboxyl derivatives are reacted with ethyl alcohol alone or with ethylates, if desired in the presence of acid-binding agents such as carbonates of monovalent or bivalent metals or pyridine. The esterification of the carboxyl group with dimethyl-aminoethanol may be carried out with or without catalysts and, if desired, the water formed may be removed by azeotropic distillation. Alternatively a salt of benzilic acid (especially an alkali salt) is reacted with a mineral acid ester of the amino-alcohol and this conversion may be carried out in hydroxyl-free solvents with the addition of anhydrous alkali carbonates. Transesterification processes may also be employed. During esterification of the carboxyl group the introduction of the nitrogen group may be effected by subsequent exchange of halogen in the esterifying group. The carboxyl group may also be esterified with amino-ethanol or a reactive ester thereof such as the chloride or sulphonic ester and the primary amino group subsequently methylated. In examples: (1) diphenyl chloracetic acid is treated with sodium and ethanol to give the ethyl ether of benzilic acid which is subsequently boiled with potassium carbonate and chlorethyl dimethylamine in acetone to give a reaction product which, on extraction with ether and hydrochloric acid successively, yields the hydrochloride of benzilic acid ethyl ether-b -dimethylaminoethyl ester; (2) the potassium salt of benzilic acid is treated with dimethylamino-ethyl chloride to form benzilic acid-b -dimethylaminoethyl ester which is treated with thionyl chloride to give diphenylchloroacetic acid - b 1 - dimethylamino-ethyl ester hydrochloride which is then dissolved in ethanol and refluxed with calcium carbonate, the reaction product being extracted as in the first example. Specification 641,571 is referred to.