Synthesis of 5-(Thiazol-5-yl)-4,5-dihydroisoxazoles from 3-Chloropentane-2,4-dione

Abstract

Condensation of 3-chloropentane-2,4-dione with thioamides gives 1-(thiazol-5-yl)ethanones and subsequent Wittig olefination, followed by nitrile oxide 1,3-dipolar cycloaddition to the resulting prop-1-en-2-yl moiety, delivers racemic 5-(thiazol-5-yl)-4,5-dihydroisoxazoles. When this thiazole and isoxazoline diheterocyclic scaffold has a carboethoxy substituent at C2 of the thiazole ring, aminolysis provides for effective diversification. A 50-member library of various 5-(thiazol-5-yl)-4,5-dihydroisoxazoles is reported.