Collect. Czech. Chem. Commun. 1987, 52, 2534-2544

2-Diethylaminoethyl esters of 1,3-disubstituted propane-2-carboxylic acids

Vladimír Valenta, Jiří Holubek, Emil Svátek, Vladimír Miller, Marie Vlková and Miroslav Protiva

Research Institute for Pharmacy and Biochemistry, 130 60 Prague 3


Alkaline hydrolysis of diethyl 1-(tetrahydro-2-furyl)-3-(1-naphthyl)propane-2,2-dicarboxylate (IV) gave the crude acid V which was purified via the dipotassium salt and was obtained as the homogeneous higher melting crystal form. Its thermic decarboxylation yielded the acid II as a mixture of two racemates (38 : 62); crystallization led to the almost homogeneous racemate B (10 : 90). Reaction of the sodium salt of II with dimethyl sulfate in methanol gave the methyl ester III which afforded by ester exchange with 2-diethylaminoethanol the ester I (mixture of two racemates 34 : 66). 2-Diethylaminoethyl 1,3-bis(1-naphthyl)propane-2-carboxylate (VII) was synthesized in three steps from diethyl (1-naphthylmethyl)malonate. Ester X was obtained from 1,3-bis(tetrahydro-2-furyl)propane-2-carboxylic acid by treatment with 2-diethylaminoethyl chloride in boiling 2-propanol in the presence of potassium carbonate. The acid V gave similarly the diester VI. 2-Diethylaminoethyl esters I, VI, VII, and X were transformed to the hydrogen oxalates. Pharmacological screening showed for the diester VI hypotensive, spasmolytic, antiarrhythmic, and antitussic activity.