Chiral Synthesis of an α-Tetrasubstituted Proline Derivative

Abstract Triple reuptake inhibitors (TRIs) have been identified as possible alternative treatments for central nervous system disorders. A practical synthesis was investigated to access a potent TRI, (4-amino-3-chloro-phenyl)-((S)-2-isobutyl-pyrrlidin-2-yl)-methanone (1), starting from alkylation of D-proline. Improved routes to key intermediates are discussed and demonstrated by an expedient multigram production of 1.