Patent GB-594294-A (GB)
Title: Manufacture of basic esters of aliphatic carboxylic acids, and the resulting products
IPC: C07D295/088
Filed: 1944-08-09
Abstract: Basic esters of aliphatic tertiary carboxylic acids having the general formula <FORM:0594294/IV/1> where R, R1 and R11 represent the same or different saturated or unsaturated aliphatic residues are prepared by reacting the acids or their halides, esters or anhydrides with amino alkanols or amino-cycloalkanols disubstituted in the amino group by two alkyl groups which in the case of the amino-alkanols may be linked together to form a heterocyclic ring, or by reacting the acids or their salts with reactive esters of the amino alcohols, if necessary in the presence of an acid-fixing agent or by reacting halogen alkyl esters of the acids with secondary aliphatic amines or secondary saturated cyclic amines wherein the nitrogen ring forms part of a heterocyclic ring.  Reactive esters which may be used include those of the halogen hydracids and aryl sulphonic acids.  The halogen alkyl esters of the tertiary acids may be prepared by reacting halogen hydrins with the tertiary carboxylic acids, their halides, esters or anhydrides, or by reacting salts of the acids with alkylene halogen hydrins and replacing the hydroxyl group in the compound obtained by halogen, or by reacting salts of the acids with alkylene dihalides.  The basic esters are stated to be novel and to have neurotropic, atropinelike action.  In examples: (1) methyl-di-n-propyl acetic acid ester of diethylamino-ethanol is prepared by reacting the amino alcohol with the chloride of the acid followed by treatment with ammonia to liberate the free basic ester, and the acid esters of dimethylamino-ethanol, dimethylamino - propanol, diethylamino - pro - panol, piperidino-ethanol, piperidino-propanol and m-dimethylamino-cyclohexanol may be prepared likewise; (2) b -diethylamino ethyl chloride is reacted with methyl-ethyl-n-butyl acetic acid in dry ethyl acetate in the presence of potash and the basic ester recovered by extraction with dilute hydrochloric acid, neutralization with potash and extraction as the free base with ether, and in like manner there are prepared diethylamino ethyl esters of ethyl-di-n-propyl acetic acid, methyl-di-isopropyl acetic acid, methyl - n - propyl - n - butyl acetic acid, dimethyl-n-amyl acetic acid, dimethyl-n-propyl acetic acid, diethyl-allyl acetic acid, methyl-n-butyl-isobutyl acetic acid, ethylidene-n-butyl acetic acid and diethyl-n-butyl acetic acid; (3) diethyl-n-butyl acetic acid chloride is reacted with ethylene chlorhydrin in the presence of pyridine and the resulting diethyl-n-butyl acetic acid-b -ethyl chloride ester heated with piperidine yielding the piperidino-ethanol ester of the diethyl-butyl acetic acid and esters are prepared likewise of methyl-di-isobutyl acetic acid, methyl-n-butyl-isobutyl acetic acid and methyl-n-propyl-n-butyl acetic acid; (4) the esters of dimethylamino-propanol and methyl-di-isobutyl acetic acid, of diethylamino-propanol and methyl-n-propyl-n-butyl acetic acid and of m-methyl-ethylamino-cyclohexanol and methyl-ethyl-n-butyl acetic acid are prepared as in (1) from the appropriate amino alcohol and acid chloride.