Convenient synthesis of (2R)- and (2S)-2-(1-methylethyl)-5-oxo-2-phenylpentanenitrile, intermediates in the preparation of phenylalkylamine calcium channel blockers

The multigram synthesis of (2S)- and (2R)-2-(1-methylethyl)-5-oxo-2-phenylpentanenitriles 9a and 9b is described, using either (4R)-2,2-dimethyl-1,3-dioxolan-4-ylmethanol or (2R)-butane-1,2,4-triol as chiral auxiliary, The configuration of an intermediate dioxolane 10b is assigned by X-ray crystallo...

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Published inJournal of the Chemical Society, Perkin Transactions 1 no. 23; pp. 2845 - 2850
Main Authors Gilmore, Jeremy, Prowse, Will, Steggles, David, Urquhart, Michael, Olkowski, Jennifer
Format Journal Article
LanguageEnglish
Published CAMBRIDGE Royal Soc Chemistry 1996
Subjects
Chemistry
Chemistry, Organic
Physical Sciences
Science & Technology
ENANTIOMERS
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Summary:The multigram synthesis of (2S)- and (2R)-2-(1-methylethyl)-5-oxo-2-phenylpentanenitriles 9a and 9b is described, using either (4R)-2,2-dimethyl-1,3-dioxolan-4-ylmethanol or (2R)-butane-1,2,4-triol as chiral auxiliary, The configuration of an intermediate dioxolane 10b is assigned by X-ray crystallography. The synthetic utility of the aldehydes is demonstrated by conversion to both enantiomers of the calcium antagonist noremopamil in >98% enantiomeric excess (ee). The enantiomeric purity of the final amines is assayed by H-1 NMR spectroscopy in the presence of the chiral solvating agent (1R)-(-)-2,2,-trifluoro-1-(9-anthryl)ethanol.
ISSN:0300-922X
1364-5463
DOI:10.1039/p19960002845