Reaction Steps
A solution of 104 (400 mg, 0.7 mmol) in dichloromethane (15 mL) was treated with BCl3 (7 mL, 7 mmol, 1M in dichloromethane) for 30 min at −60° C., then quenched with methanol (20 mL). Volatiles were distilled out to give a residue, which was dissolved into methanol (5 mL) and neutralized with Con. NH4OH (2 ml, 26% aqueous solution). After concentration, the crude product was purified by a silica gel column, eluted with 10% methanol in dichloromethane to give a mixture of the two epimers; the two epimers were separated by Prep-HPLC with the following conditions: (Agilent Prep 1200 Detecl): Column, SunFire Prep C18; mobile phase, Water with 0.05% ammonia and CH3CN; 5% CH3CN up to 100% in 8 min Detector, 220 nm to afford (3aR,5S,6S,7R,7aR)-2-(dimethylamino)-5-((S)-2-fluoro-1-hydroxyethyl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole-6,7-diol as a white solid (46.3 mg, 23%), faster eluting isomer; (ES, m/z): [M+H]+ 281.0; III NMR (300 MHz, D2O) δ 6.17 (d, J=6.6 Hz, 1H), 4.29-4.69 (m, 2H), 3.95-4.15 (m, 3H), 3.68-3.72 (m, 1H), 3.54-3.58 (m, 1H), 2.88 (s, 3H), 2.87 (s, 3H); and (3aR,5S,6S,7R,7aR)-2-(dimethylamino)-5-((R)-2-fluoro-1-hydroxyethyl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole-6,7-diol as a white solid (64 mg, 31%), slower eluting isomer; (ES, m/z): [M+H]+ 281.0; 1H NMR (300 MHz, D2O) δ 6.17 (d, 6.3 Hz, 1H), 4.44-4.57 (m, 1H), 4.28-4.39 (m, 1H), 3.92-4.12 (m, 3H), 3.67-3.72 (m, 1H), 3.27-3.49 (m, 1H), 2.89 (s, 3H), 2.87 (s, 3H).
