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Efficient preparation of an N-aryl β-amino acid via asymmetric hydrogenation and direct asymmetric reductive amination en route to Ezetimibe |
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| Authors: | Guuske F Busscher Laurent Lefort Jozef GO Cremers Marco Mottinelli Roel W Wiertz Ben de Lange Yutaka Okamura Yukinori Yusa Kazuhiko Matsumura Hideo Shimizu Johannes G de Vries André HM de Vries |
| Institution: | 1. DSM Innovative Synthesis B.V. A Unit of DSM Pharma Chemicals, PO Box 18, 6160 MD Geleen, The Netherlands;2. Takasago International Corporation, Corporate Research & Development Division, 1-4-11 Nishi-Yawata, Hiratsuka City, Kanagawa 254-0073, Japan |
| Abstract: | Two routes for the preparation of an N-aryl β-amino acid, an important precursor for the cholesterol-lowering drug Ezetimibe, were investigated. The first pathway proceeds via an Rh- or Ir-catalyzed asymmetric hydrogenation of N-aryl enamine giving the desired product with up to 82% ee. The other pathway involves a direct asymmetric reductive amination (DARA) of the β-keto ester which yielded the β-amino ester in high yield and 97% ee. Subsequent copper-catalyzed N-arylation gave the target compound. |
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