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

(R)- and (S)-2-bromo-1-(4-nitrophenyl)ethanol are precursors of important P-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. (C) 2005 Elsevier Ltd. All rights reserved.