Preparation of lamivudine impurity A lamivudine acid: 100 ml of methanol-water solution (1:1) was added to a 250 ml round-bottomed flask, 50 ml of 25% aqueous sodium hydroxide solution was added, and 5S-cytosine-1’- 1,3-oxathiolane-2-carboxylic acid-(1’R,2’S,5’R) menthyl ester (CME) 20g, stirred at 25. The reaction was carried out for 5 h. When the solution was clarified, the reaction was stopped, the organic phase was removed by extraction with dichloromethane, the aqueous phase was collected, the pH was adjusted to 3-4 with dilute hydrochloric acid solution under stirring at 0-5C, and after stirring for about 20 min, a pale white solid was precipitated, filtered, washed with water, dried and recrystallized to obtain the white crystalline powder lamivudine impurity A, i.e.: (2R-cis)-5-(4-aMino-2-oxo-1(2H)-pyriMidinyl)-1,3-oxathiolane-2-carboxylic Acid (abbreviation: lamivudine acid), HPLC purity >98%.
