Ru-catalyzed C-H arylation has aroused a keen interest in the synthesis of biaryls due to high atom economy. However, most of the protocols hitherto reported have required high catalyst loading (5 to 10 mol%) and often suffered from lack of reproducibility especially in scale. During our process development of angiotensin II receptor blockers (ARBs) using C-H arylation,1-5 same kind of issues have arisen and seriously retarded further development to multihundred kilograms scale production. To address the challenge, we searched for a better catalytic system having a new cocatalyst to ensure robustness of the C-H arylation. Disclosed herein is a highly efficient protocol for the C-H arylation employing a novel cocatalyst (K 2, 4, 6-trimethylbenzenesulfonate, TMBSK) and the application to a practical synthesis of Candesartan Cilexetil.6-10 References Seki, M. WO2011061996, 2010. Seki, M. ACS Catal. 2011, 1, 607. Seki, M. Nagahama, M. J. Org. Chem. 2011, 76, 10198. Seki, M. Synthesis 2012, 44, 3231. Seki, M. J. Syn. Org. Chem. Jpn. 2012, 70, 1295. Seki, M. RSC Adv. 2014, 4, 29131. Seki, M. Synthesis, in press (DOI: 10.1055/s-0034-1378585). Seki, M. ACS Catal., in press (DOI: (10.1021/cs501328x). Seki, M. WO2014034868, 2014. Seki, M. WO2014051008, 2014.

Efficient catalytic system for Ru-catalyzed C-H arylation: A practical synthesis of a pharmaceutical

249th National Meeting (2015)

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