1,3-oxathiolan-5-ones useful in the production of antiviral nucleoside analogues

The present invention relates to commercial processes for the production of antiviral 1,3-oxathiolane nucleoside analogues including, but not limited to, cis(−)-4-amino-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-2(1H)-pyrimidinone (emtricitabine, (−)-FTC, 1) and cis(−)-4-amino-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-2(1H)-pyrimidinone (lamivudine, 3TC, 2). In one embodiment, the present invention relates to novel crystalline intermediates useful in the preparation of antiviral 1,3-oxathiolane nucleoside analogues in enantiomerically enriched form, and to commercial processes for their preparation. A compound of the formula A, wherein R* is a chiral auxiliary, and where the configuration at the asymmetric carbon atom between oxygen and sulfur is (R), (S), or combinations of (R) and (S), useful in the preparation of enantiomerically enriched 1,3-oxathiolane nucleoside analogues, for example (−)-FTC and 3TC.