Stereochemistry of metabolism of amphetamines: use of (-)-alpha-methoxy-alpha-(trifluoromethyl)phenylacetyl chloride for GLC resolution of chiral amines.

Amphetamine and eight related compounds were reacted with the chiral acylating reagent (-)-alpha-methoxy-alpha-(trifluoromethyl)phenylacetyl chloride to obtain, in each case, two diastereomeric amide derivatives. GLC conditions were found for the separation of the diastereomers in seven of the nine cases studied. This procedure may be suitable for the resolution of amino acid enantiomers via the amide derivatives of the methyl esters. Secondary amines were not derivatized under the reaction conditions used. A correlation between absolute configuration and elution order of the diastereomeric amides was observed for five compounds. The chiral acylating reagent was used in the determination of the enantiomeric composition of 2,5-dimethoxy-4-methylamphetamine excreted in rat urine after intraperitoneal drug administration. The chiral acylating reagent is suitable for the determination of the optical composition of compounds extracted from biological fluids.