Optical resolution and determination of absolute configuration of nipradilol.

Abstract

It was confirmed that the title compound, a new antihypertensive drug, consists of four optical isomers : two diastereomers and their enantiomers. Separation of the diastereomers was effected by recrystallization. Optical resolution of the enantiomers was carried out by repeated recrystallization of their diastereomeric salts with (+)-or (-)-2-[1-(p-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl] acetoxy-2-phenylacetic acid or by high performance liquid chromatography of the L-menthoxyacetyl derivatives. The absolute configurations of the separated isomers were determined on the basis of the circular dichroism spectra and proton nuclear magnetic resonance spectra.