A METHOD OF PREPARATION OF N-(1-OXOPENTYL)-N-[[2'-(1H-TETRAZOL-5-y1) [1,1'-BIPHENYL] -4-y1]METHYL]-L-VALINE (VALSARTAN)

摘要

From the starting 4-bromomethyl-2'-(1-triphenylmethyltetrazol-5-yl)biphenyl, N-[(2'­(1-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl)methyl]-(L)-valine benzyl ester of formula 7 is obtained via a reaction with L-valine benzyl ester, and is converted to valsartan of formula I via a reaction with valeryl chloride and removing of protective groups. The method consists in converting, with hydrochloric acid, N-[(2'-(l-triphenylmethyl-tetrazol-5-yl)biphenyl-4­yl)methyl]-(L)-valine benzyl ester of formula 7, obtained in the first stage, to N-[(2'-(1-­triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl)methyl]-(L)-valine benzyl ester hydrochloride of formula III, which is optionally re-crystallized.