Synthesis of β-adrenergic blockers ( R)-(−)-nifenalol and ( S)-(+)-sotalol via a highly efficient resolution of a bromohydrin precursor

Abstract

( R)- and ( S)-2-bromo-1-(4-nitrophenyl)ethanol are precursors of important β-adrenergic receptor blocking drugs ( R)-nifenalol and ( S)-sotalol, respectively. Both were obtained in enantiomeric pure forms via a single highly efficient enzymatic transesterification reaction of (±)-2-bromo-1-(4-nitrophenyl)ethanol using immobilized lipase PS-C-II ( E >1000; concn 200 g/L), while PS lipase completely failed to react. On the other hand, the hydrolytic method also produced enantiorich precursors though relatively less efficient (PS-C-II, E = 5.1). Out of all the approaches employed the transesterification method proved to be the most efficient.