Synthesis of 4-aryl-2-pyrrolidones and β-aryl-γ-amino-butyric acid (GABA) analogues by heck arylation of 3-pyrrolines with arenediazonium tetrafluoroborates.: Synthesis of (±)-rolipram on a multigram scale and chromatographic resolution by semipreparative chiral simulated moving bed chromatography

We report herein a new, practical, and economic synthesis of the phosphodiesterase inhibitor Rolipram on a multigram. scale as well as the synthesis of new 4-aryl pyrrolidones and beta-aryl-gamma-amino butyric acids (GABA derivatives) employing an efficient Heck-Matsuda arylation of 3-pyrroline with aryldiazonium tetrafluoroborates. Racemic Rolipram was resolved into its enantiomers using chiral simulated moving bed chromatography having the low-cost microcrystalline cellulose triacetate as a chiral stationary phase.