Reaction Steps
tert-Butyl[(4aR,6R,8aS)-8a-(2,4-difluorophenyl)-6-(hydroxymethyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]carbamate (C24) (82 mg, 0.20 mmol) was dissolved in a mixture of acetonitrile (0.8 mL) and tetrahydrofuran (0.2 mL). 1,1,2,2,3,3,4,4,4-Nonafluorobutane-1-sulfonyl fluoride (71.1 μL, 0.396 mmol) was added, followed by triethylamine trihydrofluoride (64.4 μL, 0.395 mmol), and then triethylamine (0.166 mL, 1.19 mmol), and the reaction mixture was allowed to stir at room temperature for 18 hours. Saturated aqueous sodium bicarbonate solution was added, and the mixture was extracted three times with dichloromethane. The combined organic extracts were washed with water, washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated in vacuo. Purification via preparative thin layer chromatography on silica gel (Eluent: 5% methanol in dichloromethane) afforded the product as a pale yellow foam. Yield: 22 mg, 0.053 mmol, 27%. LCMS m/z 415.4 (M−1). 1H NMR (400 MHz, CDCl3), characteristic peaks: δ 1.53 (s, 9H), 1.87-1.99 (m, 1H), 2.57 (dd, J=12.9, 2.8 Hz, 1H), 2.93 (dd, J=12.9, 3.8 Hz, 1H), 3.01-3.10 (br m, 1H), 3.79 (br d, J=12 Hz, 1H), 3.91-4.03 (m, 1H), 4.15 (dd, J=11.9, 1.9 Hz, 1H), 4.42 (ddd, half of ABXY pattern, J=46.7, 9.9, 3.6 Hz, 1H), 4.50 (ddd, half of ABXY pattern, J=47.7, 9.9, 6.4 Hz, 1H), 6.85 (ddd, J=12.4, 8.4, 2.4 Hz, 1H), 6.89-6.96 (m, 1H), 7.28-7.36 (m, 1H).
