A Novel Method for Large-Scale Synthesis of Lamivudine through Cocrystal Formation of Racemic Lamivudine with (<i>S</i>)-(−)-1,1′-Bi(2-naphthol) [(<i>S</i>)-(BINOL)]

Abstract

A large-scale synthesis of (−)-[2R,5S]-4-amino-1- [2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-2(1H)-pyrimidin-2-one (lamivudine) through resolution of racemic lamivudine by cocrystal formation with (S)- BINOL has been demonstrated. Lamivudine of very high purity with an enantiomeric excess of more than 99.9% was obtained. All four isomers of lamivudine have also been separated and characterized. Interestingly, cis-(−)- and trans-(−)-enantiomers form cocrystals with (S)-BINOL.