A Chemoenzymatic Dynamic Kinetic Resolution Approach to Enantiomerically Pure (R)- and (S)-Duloxetine
- 31 March 2011
- journal article
- research article
- Published by American Chemical Society (ACS) in The Journal of Organic Chemistry
- Vol. 76 (10) , 3917-3921
- https://doi.org/10.1021/jo2003665
Abstract
The synthesis of (R)-duloxetine is described. Dynamic kinetic resolution of β-hydroxynitrile rac-1 using Candida antarctica lipase B (CALB, N435) and ruthenium catalyst 6 afforded β-cyano acetate (R)-2 in high yield and in excellent enantioselectivity (98% ee). The subsequent synthetic steps were straightforward and (R)-duloxetine was isolated in 37% overall yield over 6 steps. The synthetic route also constitute a formal total synthesis of (S)-duloxetine.Keywords
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