Chiral separation of beta-blockers after derivatization with (-)-(alpha)-methoxy-alpha-(trifluoromethyl)phenylacetyl chloride by gas chromatography

Abstract

Gas chromatographic method was investigated for the chiral separation of several P-blockers(atenolol, betaxolol, bisoprolol, metoprolol and pindolol) using (-)-alpha -methoxy-alpha-(trifluoromethyl)phenylacetyl chloride as a chiral derivatizing agent for amino group. Prior to N-acylation, hydroxyl group was converted into O-silyl ethers by react with N-methyl-N-(trimethylsilyl)trifluoroacetamide. The reaction was selective and rapid and the diastereomeric derivatives were well separated by capillary gas chromatography. (R)-isomers were eluted faster than (S)-isomers when (-)-alpha -methoxy-alpha-(trifluoromethyl)phenylacetyl chloride was used as the chiral derivatizing agent. But in the opposite sequence when (+)-alpha -methoxy-alpha-(trifluoromethyl) phenylacetyl chloride was used. No racemization was found during the reaction.