Alternative Synthesis of Isoguvacine and Its N-(2-Aryl-2-hydroxyethyl) Derivatives

Abstract

Isonicotinic acid ethyl ester reacted with substituted phenacyl bromides to give the corresponding quaternary salts which were reduced with sodium tetrahydridoborate to ethyl 1-(2-aryl-2-hydroxyethyl)-1,2,3,6- tetrahydropyridine-4-carboxylates. The presence of an electron-donating substituent in the benzene ring of the latter is a necessary condition for their acid hydrolysis with cleavage of the C–N bond and formation of isoguvacine. Analogous derivatives with electron-withdrawing substituents are not converted to isoguvacine under similar conditions.