title: Synthesis of valsartan via decarboxylative biaryl coupling.
abstract: An efficient synthesis of the angiotensin II inhibitor valsartan (Diovan) is presented. Two routes were evaluated, both making use of an advanced version of our decarboxylative coupling for the construction of the biaryl moiety. Thus, in the presence of a catalyst system consisting of copper(II) oxide, 1,10-phenanthroline, and palladium(II) bromide, 2-cyanocarboxylic acid was coupled with 1-bromo(4-dimethoxymethyl)benzene in 80% yield and with 4-bromotoluene in 71% yield. The valsartan synthesis using 1-bromo(4-dimethoxymethyl)benzene was completed in four steps overall with a total yield of 39%, via a novel route that presents substantial economical and ecological advantages over the literature process, as it is more concise and stoichiometric amounts of expensive organometallic reagents are avoided.
authors: Institut für Organische Chemie, TU Kaiserslautern, Erwin-Schrödinger-Strasse, D-67663 Kaiserslautern, Germany. goossen@chemie.uni-kl.de
authors: Lukas J
authors: LJ
authors: Goossen
authors: Bettina
authors: B
authors: Melzer
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000138:chemical synthesis; D001555:Benzene Derivatives / Q000138:chemical synthesis / Q000737:chemistry; D013777:Tetrazoles / Q000138:chemical synthesis*; D014633:Valine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D000068756:Valsartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001555:Benzene Derivatives; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine