Synthesis of a Novel Angiotensin II Receptor Antagonist Olmesartan Medoxomil

In this paper, a new angiotensin Ⅱ receptor antagonist, (5-methyl-2-oxo-1,3-dioxol-4-yl) methyl-4-(1-hydroxy-1-methylethyl)-2-propyl-1-[(2′-1H-tetrazol-5-yl-biphenyl-4-yl) methyl] imdazole-5-carboxylate(Olmesartan medoxomil), was synthesized using tartaric acid as starting material via nitration, cyclization, esterifcation, Grignard reaction, N-alkylation, hydrolyzation, O-alkylation and N-deprotection in 32.7% overall yield. The structure of title compound has been characterized by MS(mass spectrum), (()~1H)-NMR (nuclear magnetic resonance) and IR (ifrared spectrum). The condensation of 4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylic acid ethyl ester with 5-[4′-(bromomethyl) biphenyl-2-yl]-1-(triphenylmethyl) tetrazole by means of potassium hydroxide in DMF, instead of potassium tert-butoxide in dimethylacetamide or sodium hydroxide in DMF, gives the corresponding N-alkylated product, which is hydrolyzed with sodium hydroxide, instead of lithium hydroxide, in dioxane-water to the desired acid. The improved process is more practical.