Diisopropylethylamine → N-((2'-Cyano(1,1'-biphenyl)-4-yl)methyl)-L-valine methyl ester

Participants

Reaction Steps

Bioorganic & Medicinal Chemistry Letters (1994), 4(1), 29-34, reported a process for the preparation of Valsartan by reacting 4′-bromomethyl-2-cyanobiphenyl (II) with (L)-valine methyl ester hydrochloride (V) in the presence of diisopropylethylamine in methylenechloride to produce N-[(2′-cyanobiphenyl-4-yl)methyl]-(L)-valine methyl ester (VI), followed by reacting with valeryl chloride in the presence of diisopropylethylamine in methylenechloride to produce N-valeryl-N-[(2′-cyanobiphenyl-4-yl)methyl]-(L)-valine methyl ester (VII), which is further reacted with tributyltin azide in xylene to produce N-[[2′-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-N-valeryl-(L)-valine methyl ester (VIII), followed by hydrolysis with aqueous base to produce Valsartan of formula (I).

Provenance & Evidence