Synthesis 2012; 44(20): 3231-3237
DOI: 10.1055/s-0032-1317131
paper
© Georg Thieme Verlag Stuttgart · New York

An Efficient C–H Arylation of a 5-Phenyl-1H-tetrazole Derivative: A Practical Synthesis of an Angiotensin II Receptor Blocker

Masahiko Seki*
Mitsubishi Tanabe Pharma Corporation, 2-6-18, Kitahama, Chuo-ku, Osaka 541-8505, Japan, Fax: +81(6)62013150   Email: seki.masahiko@mm.mt-pharma.co.jp
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Further Information

Publication History

Received: 28 June 2012

Accepted after revision: 26 July 2012

Publication Date:
21 August 2012 (online)


Abstract

An efficient protocol for C–H arylation of 1-benzyl-5-phenyl-1H-tetrazole has been developed which involves an extremely small amount of commercially available [RuCl2(p-cymene)]2 (Ru: 0.63 mol%) and a specific amount of triphenylphosphine (ratio Ph3P/Ru 2:1). The obtained biphenyl derivative was readily elaborated to give candesartan cilexetil, a potent angiotensin II receptor blocker by means of an efficient removal of the benzyl protecting group by palladium on carbon catalyzed transfer hydrogenation in the final step.