Efficient preparation of an N-aryl β-amino acid via asymmetric hydrogenation and direct asymmetric reductive amination en route to Ezetimibe

Guuske F. Busscher; Laurent Lefort; Jozef G.O. Cremers; Marco Mottinelli; Roel W. Wiertz; Ben de Lange; Yutaka Okamura; Yukinori Yusa; Kazuhiko Matsumura; Hideo Shimizu; Johannes G. de Vries; André H.M. de Vries

doi:10.1016/j.tetasy.2010.04.013

Efficient preparation of an N-aryl β-amino acid via asymmetric hydrogenation and direct asymmetric reductive amination en route to Ezetimibe

Guuske F. Busscher
, Laurent Lefort
, Jozef G.O. Cremers
, Marco Mottinelli
, Roel W. Wiertz
, Ben de Lange
, Yutaka Okamura
, Yukinori Yusa
, Kazuhiko Matsumura
, Hideo Shimizu
, Johannes G. de Vries
, André H.M. de Vries

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Pages (from-to)	1709-1714
Number of pages	6
Journal	Tetrahedron Asymmetry
Volume	21
Issue number	13
DOIs	https://doi.org/10.1016/j.tetasy.2010.04.013
Publication status	Published - 2010

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Busscher, G. F., Lefort, L., Cremers, J. G. O., Mottinelli, M., Wiertz, R. W., Lange, B. D., Okamura, Y., Yusa, Y., Matsumura, K., Shimizu, H., Vries, J. G. D., & Vries, A. H. M. D. (2010). Efficient preparation of an N-aryl β-amino acid via asymmetric hydrogenation and direct asymmetric reductive amination en route to Ezetimibe. Tetrahedron Asymmetry, 21(13), 1709-1714. https://doi.org/10.1016/j.tetasy.2010.04.013

@article{331d335012ae454fa73d6291a4abb3d7,

title = "Efficient preparation of an N-aryl β-amino acid via asymmetric hydrogenation and direct asymmetric reductive amination en route to Ezetimibe",

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.",

author = "Busscher, \{Guuske F.\} and Laurent Lefort and Cremers, \{Jozef G.O.\} and Marco Mottinelli and Wiertz, \{Roel W.\} and Lange, \{Ben de\} and Yutaka Okamura and Yukinori Yusa and Kazuhiko Matsumura and Hideo Shimizu and Vries, \{Johannes G. de\} and Vries, \{Andr{\'e} H.M. de\}",

note = "Relation: http://www.rug.nl/scheikunde/onderzoek/scholen/stratingh/index date\_submitted:2010 Rights: University of Groningen, Stratingh Institute for Chemistry",

year = "2010",

doi = "10.1016/j.tetasy.2010.04.013",

language = "English",

volume = "21",

pages = "1709--1714",

journal = "Tetrahedron Asymmetry",

issn = "0957-4166",

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Busscher, GF, Lefort, L, Cremers, JGO, Mottinelli, M, Wiertz, RW, Lange, BD, Okamura, Y, Yusa, Y, Matsumura, K, Shimizu, H, Vries, JGD & Vries, AHMD 2010, 'Efficient preparation of an N-aryl β-amino acid via asymmetric hydrogenation and direct asymmetric reductive amination en route to Ezetimibe', Tetrahedron Asymmetry, vol. 21, no. 13, pp. 1709-1714. https://doi.org/10.1016/j.tetasy.2010.04.013

TY - JOUR

T1 - Efficient preparation of an N-aryl β-amino acid via asymmetric hydrogenation and direct asymmetric reductive amination en route to Ezetimibe

AU - Busscher, Guuske F.

AU - Lefort, Laurent

AU - Cremers, Jozef G.O.

AU - Mottinelli, Marco

AU - Wiertz, Roel W.

AU - Lange, Ben de

AU - Okamura, Yutaka

AU - Yusa, Yukinori

AU - Matsumura, Kazuhiko

AU - Shimizu, Hideo

AU - Vries, Johannes G. de

AU - Vries, André H.M. de

N1 - Relation: http://www.rug.nl/scheikunde/onderzoek/scholen/stratingh/index date_submitted:2010 Rights: University of Groningen, Stratingh Institute for Chemistry

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

U2 - 10.1016/j.tetasy.2010.04.013

DO - 10.1016/j.tetasy.2010.04.013

M3 - Article

SN - 0957-4166

VL - 21

SP - 1709

EP - 1714

JO - Tetrahedron Asymmetry

JF - Tetrahedron Asymmetry

IS - 13

ER -

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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