CONVENIENT SYNTHESIS OF 2R)-2-(1-METHYLETHYL)-5-OXO-2-PHENYLPENTANENITRILE AND S)-2-(1-METHYLETHYL)-5-OXO-2-PHENYLPENTANENITRILE, INTERMEDIATES IN THE PREPARATION OF PHENYLALKYLAMINE CALCIUM-CHANNEL BLOCKERS

The multigram synthesis of (2S)- and R)-2-(1-methylethyl)-5-oxo-2-phen ylpentanenitriles 9a and 9b is described, using either (4R)-2,2-dimeth yl-1,3-dioxolan-4-ylmethanol or (2R)-butane-1,2,4-triol as chiral auxi liary, The configuration of an intermediate dioxolane 10b is assigned by X-ray crystallography. The synthetic utility of the aldehydes is de monstrated 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 presenc e of the chiral solvating agent (1R)-(-)-2,2,-trifluoro-1-(9-anthryl)e thanol.