Chiral separation of β-blockers after derivatization with (-)-α-Methoxy-α-(trifluoromethyl)phenylacetyl chloride by gas chromatography

Gas chromatographic method was investigated for the chiral separation of several β-block-ers(atenolol, betaxolol, bisoprolol, metoprolol and pindolol) using (-)-α-methoxy-α-(trifluoromethyl)phenylacetyl chloride as a chiral derivatizing agent for amino group. Prior to N-acylation, hydroxyl group was converted intoO-silyl ethers by react withN-methyl-N-(tri-methylsilyl)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 (-)-α-methoxy-α-(trifluoromethyl)phenylacetyl chloride was used as the chiral derivatizing agent. But in the opposite sequence when (+)-α-methoxy-α-(trifluoromethyl)phenylacetyl chloride was used. No racemization was found during the reaction.