Synthesis of racemic and chiral Carvedilolstarting from corresponding5-(chloromethyl)oxazolidin-2-one

摘要

The synthesis of racemic Carvedilol ((±)-l) has been achieved starting from 2-(chloromethyl) oxirane ((±)-2) in a four-step sequence. 5-(Chloromethyl) oxazolidin-2-one ((±)-3) and 5-((9H-carbazol-4-yloxy) methyl) oxazolidin-2-one ((±)-4) are intermediates. A similar sequence starting from (R)- or (S)-2-(chloromethyl)oxirane 2 give corresponding chiral 5-((9H-carbazol-4-yloxy)methyl) oxazolidin-2-one 4 followed by chiral Carvedilol 1. The synthetic sequence followed avoids the formation of impurity B (bis impurity). This approach can be useful for the preparation of pharmaceutically important moieties containing p-amino alcohols without formation of bis impurity.