Novel Syntheses of 2-Butyl-5-chloro-3<i>H</i>-imidazole-4-carbaldehyde:  A Key Intermediate for the Synthesis of the Angiotensin II Antagonist Losartan

Abstract

Reaction of glycine methyl ester (19) with imidate 18 under carefully optimized conditions allowed preparation of the rather unstable imidazolinone 11 in ca. 90% yield. Reaction of 11 with POCl(3)/DMF followed by aqueous workup gave aldehyde 2, a key intermediate for the synthesis of the angiotensin II antagonist Losartan, in ca. 55% yield. Structural identification of intermediates and byproducts formed during both the reaction to prepare 11 and the reaction of 11 with POCl(3)/DMF allowed development of several closely related syntheses of aldehyde 2.