Reaction Steps
A solution of 99 (600 mg, 1 mmol) in dichloromethane (20 mL) was treated with BCl3 (10 mL, 10 mmol, 1 M in dichloromethane) for 1 hour at −78° 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 40% in 8 min; Detector, 220 nm) to afford (3aR,5S,6S,7R,7aR)-5-((S)-2,2-difluoro-1-hydroxyethyl)-2-(dimethylamino)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole-6,7-diol as a light yellow solid (14.4 mg, 5%), faster eluting isomer; (ES, m/z) [M+H]+ 299.0, 1H NMR (300 MHz, D2O) δ 6.19 (d, J=6.6 Hz, 1H), 5.71-6.09 (m, 1H), 4.15 (t, J=6.0 Hz, 1H), 3.89-3.99 (m, 2H), 3.78-3.82 (m, 1H), 3.37 (t, J=8.7 Hz, 1H), 2.89 (s, 6H); and (3aR,5S,6S,7R,7aR)-5-((R)-2,2-difluoro-1-hydroxyethyl)-2-(dimethylamino)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole-6,7-diol as a light yellow solid (53.9 mg, 17.4%), slower eluting isomer; (ES, m/z) [M+H]+ 299.0, 1H NMR (300 MHz, D2O) δ 6.20 (d, J=6.3 Hz, 1H), 5.62-6.00 (m, 1H), 4.07 (t, J=6.0 Hz, 1H), 3.87-3.96 (m, 2H), 3.72-3.77 (m, 1H), 3.62-3.65 (m, 1H), 2.88 (s, 6H).
