To a solution of chiral 1-((2R,3R,4S,5S)-3,5-difluoro-4-hydroxy-5-(hydroxymethyl)-3-methyltetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione (60 mg, 216 μmol) prepared in Preparation 6 in THF (8 ml) was added a THF solution (Aldrich, 1 M) of tert-butylmagnesium chloride (539 μl, 539 μmol) dropwise. The mixture was stirred at room temperature for 15 min. followed by the addition of THF solution (0.5 M) of (2S)-isopropyl 2-(chloro(naphthalen-2-yloxy)phosphorylamino)propanoate (1.08 mL, 539 μmol). The reaction mixture was stirred at room temperature for 1 h, then additional THF solution (Aldrich, 1 M) of tert-butylmagnesium chloride (270 μl, 270 μmol) and THF solution (0.5 M) of (2S)-isopropyl 2-(chloro(naphthalen-2-yloxy)phosphorylamino)propanoate (0.54 mL, 270 μmol) were added. The reaction mixture was then stirred at room temperature for 18 h. Methanol (2 mL) was added to quench the reaction. The mixture was purified by flash chromatography (silica gel, 1-18% MeOH in DCM) and dried in vacuo to give the title compound as a white solid (75 mg, 58%).
