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

A large-scale synthesis of (−)-[2 R,5 S ]-4-amino-1- [2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-2(1 H )-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.