Reaction Steps
2-Propanol (139 μL, 1.82 mmol) was added to a suspension of sodium hydride (60% in mineral oil, 29 mg, 0.73 mmol) in tetrahydrofuran (3 mL), and the mixture was stirred for 30 minutes. A solution of N-[(4R,4aR,6R,8aS)-6-(bromomethyl)-8a-(2,4-difluorophenyl)-4-methyl-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide (C26) (90 mg, 0.18 mmol) in tetrahydrofuran (0.5 mL) was added, and the reaction mixture was heated at 55° C. for 6 hours. After cooling to room temperature, it was partitioned between saturated aqueous ammonium chloride solution (20 mL) and ethyl acetate (25 mL). The aqueous layer was extracted with ethyl acetate (2×25 mL), and the combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Silica gel chromatography (Gradient: 0% to 70% ethyl acetate in heptane) provided the product as a white solid. Yield: 39.2 mg, 82.4 μmol, 46%. 1H NMR (400 MHz, CD3OD) δ 8.12 (br d, J=7 Hz, 2H), 7.51-7.57 (m, 1H), 7.39-7.49 (m, 3H), 7.01-7.11 (m, 2H), 4.14 (br d, J=12 Hz, 1H), 3.89 (d, J=11.9 Hz, 1H), 3.78-3.85 (m, 1H), 3.67 (septet, J=6.0 Hz, 1H), 3.48-3.58 (m, 2H), 3.19-3.28 (br m, 1H), 2.96-3.04 (m, 1H), 1.75-1.82 (m, 1H), 1.51-1.64 (m, 1H), 1.25 (d, J=7.0 Hz, 3H), 1.14 (d, J=6.0 Hz, 3H), 1.14 (d, J=6.0 Hz, 3H).
