Reaction Steps
To a solution of 119 (4.5 g, 9 mmol) in 1,4-dioxane (50 mL) was added Pd(PPh3)4 (2.1 g, 1.8 mmol), Et3N (23 g, 22.7 mmol) and HCOOH (0.8 g, 18 mmol) at 25° C. under N2 atmosphere. After 20 min at 60° C., additional HCOOH (6.3 g, 136 mmol) was added and the mixture was stirred for additional 12 hours at 60° C., then quenched by H2O (60 mL), extracted with dichloromethane (2×40 mL) to remove the organic impurities. The pH value of aqueous phase was adjusted to 7-8 by saturated aqueous NaHCO3, then concentrated under reduced pressure to give a residue, which was purified by a silica gel column, eluted with 2%-10% methanol in dichloromethane to give the mixture of the two epimer. Further separation by Prep HPLC [(Agilent 1200 prep HPLC): Column, Sun Fire Prep C18*50 mm 5 um; mobile phase, WATER with CH3CN (5% CH3CN up to 40% in 10 min); Detector, UV, 220 nm] to afford (3aR,5S,6S,7R,7aR)-2-(methylamino)-5-((S)-1,1,1-trifluoro-2-hydroxypropan-2-yl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole-6,7-diol as white solid (730 mg, 25.4%), Faster eluting isomer. (ES, m/z): 317.0; 1HNMR (300 MHz, D2O) δ 6.27 (d, J=6.9 Hz, 1H), 4.38-4.41 (m, 1H), 4.22-4.23 (m, 1H), 3.94-3.97 (d, J=8.4 Hz, 1H), 3.56-3.60 (d, J=8.4 Hz, 1H), 2.77 (s, 3H), 1.34 (s, 31-1); and (3aR,5S,6S,7R,7aR)-2-(methylamino)-5-(1,1,1-trifluoro-2-hydroxypropan-2-yl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole-6,7-diol as white solid (810 mg, 28.2%), Slower eluting isomer. (ES, m/z): 317.0; 1HNMR (300 MHz, D2O) δ 6.26 (d, J=6.9 Hz, 1H), 4.37-4.39 (m, 1H), 4.18-4.20 (m, 1H), 3.96-3.99 (m, 1H), 3.60-3.62 (d, J=8.4 Hz, 1H), 2.77 (s, 3H), 1.33 (s, 3H).
