GB782055A - Process for the manufacture of alkylaminobenzoic acid esters or salts thereof - Google Patents

Abstract

Esters of alkylamino benzoic acids of the formula <FORM:0782055/IV (a)/1> and acid addition salts thereof, in which R1 and R2 may be hydrogen or lower alkyl, aralkyl or cycloalkyl groups or together with the nitrogen form a heterocyclic radical, R3 is a hydrogen atom or a lower alkyl group and R4 represents a lower alkyl group are made by reacting a 1 - amino - 3 - halogen - propanol - (2) of the formula <FORM:0782055/IV (a)/2> with an aminobenzoic acid of the formula <FORM:0782055/IV (a)/3> or an alkali metal salt of the acid or by reacting the amino-halogen-propanol with a corresponding nitrobenzoic acid and converting the resulting nitro-compound into the desired amino-compound by reduction and alkylation. Aralkyl radicals present at the terminal amine group of the reaction products may, if desired, be split off by catalytic hydrogenation. The esterification reaction is suitably carried out in solution or suspension in a solvent such as a lower aliphatic alcohol and in particular, isopropyl alcohol. In examples: (1) and (2) propylaminobenzoic acid is treated with g -dimethylamino-b -hydroxypropyl chloride to give p-propylamino-benzoic acid g -dimethylamino-b -hydroxypropyl ester which may be converted into its hydrochloride; (3) p-propylamino-benzoic acid is treated with g -piperidino-b -hydroxy-propyl chloride to give p-propylamino-benzoic acid g -piperidino-b -hydroxypropyl ester as its hydrochloride; (4) p-butylaminobenzoic acid is treated with g -benzylmethylamino-b -hydroxy-propyl chloride to give p-butylamino-benzoic acid g -benzylmethylamino-b -hydroxypropyl ester as its hydrochloride; (5) p-butylaminobenzoic acid is treated with g -benzylcyclohexylamino-b -hydroxy-propyl chloride and the product is treated with hydrogen in the presence of palladium to give p-butylaminobenzoic acid g - cyclohexylamino - b - hydroxypropyl ester as its hydrochloride; (6) p-nitro-benzoic acid is treated with g -dimethylamino-b -hydroxypropyl bromide, the resulting p-nitrobenzoic acid g -dimethylamino-b -hydroxypropyl ester, which is separated as the hydrochloride, is reduced with palladium and hydrogen to give b -aminobenzoic g -dimethylamino b -hydroxypropyl ester hydrochloride which is treated with propionaldehyde and reduced with palladium and hydrogen to give p-propylaminobenzoic acid g -dimethylamino-b -hydroxypropyl ester; (7) p-butylaminobenzoic acid is treated with g -dibenzylamino-b -hydroxypropyl chloride and the resulting p-butylaminobenzoic acid g -dibenzylamino-b -hydroxypropyl ester hydrochloride is reduced with palladium and hydrogen to give g -amino-b -hydroxypropyl ester; (8) p-diethylaminobenzoic acid is reacted with g -dimethylamino-b -hydroxypropyl chloride to give p-diethylaminobenzoic acid g -dimethylamino-b -hydroxypropyl ester hydrochloride; and (9) o-butylamino-benzoic acid is treated with g -dimethylamino-b -hydroxypropyl chloride to give o-butylamino-benzoic acid g -dimethylamino-b -hydroxypropyl ester hydrochloride.