Microwave-Assisted Synthesis of(±)-Mandelic Acid-d5, Optical Resolution, and Absolute Configuration Determination

An efficient microwave-assisted synthesis of(±)-mandelic acid-d5was developed. The racemic mixture was resolved by diastereomeric salt formation using 1-phenylethylamine enantiomers as resolving agents. At each step, the resolution process was checked by determining mandelic acid-d5enantiomer ee values directly on fractional crystallized diastereomeric salts by chiral capillary electrophoresis analysis. Highly enriched (−)- and (+)-mandelic acid-d5(95% and 90% ee, resp.) were obtained and their absolute configurations—RandS, respectively—were determined by correlation of the (−)-mandelic acid-d5circular dichroism spectrum to the (R)-mandelic acid one.