Diastereoselective, large scale synthesis of beta -amino acids via asymmetric enamide hydrogenation as alpha 2 delta ligands for the treatment of generalized anxiety disorder and insomnia

The syntheses of beta -amino acids 1 and 2 are presented by means of an alternative route to the asymmetric Michael-addition route reported in the preceding article. These two compounds, which bind to the alpha 2 delta subunit of calcium channels and have important medical applications, have been pr...

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Bibliographic Details
Published in:Tetrahedron letters 2009-11, Vol.50 (46), p.6329-6331
Main Authors: Magano, Javier, Conway, Brian, Bowles, Daniel, Nelson, Jade, Nanninga, Thomas N, Winkle, Derick D, Wu, Haifeng, Chen, Michael H
Format: Article
Language:English
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Summary:The syntheses of beta -amino acids 1 and 2 are presented by means of an alternative route to the asymmetric Michael-addition route reported in the preceding article. These two compounds, which bind to the alpha 2 delta subunit of calcium channels and have important medical applications, have been prepared on multi- kilogram scale in our pilot plant through a new approach that introduces the chirality at the beta -carbon via asymmetric hydrogenation of an enamide precursor. Two Rh-based catalysts, (R)-mTCFP-Rh(COD)BF sub(4) and (R)-binapine-Rh(COD)BF sub(4), were found to be superior in this transformation and gave very high diastereoselectivities. The process development for catalyst selection is described.
ISSN:0040-4039
DOI:10.1016/j.tetlet.2009.08.111