反应详情

温度

0 °C

Boron trifluoride diethyl etherate (21 μL, 0.98 mmol) was added to a solution of N-[(4aR,6R,8aS)-8a-(2,4-difluorophenyl)-6-(1-hydroxy-4-methylpent-4-en-1-yl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide (C77) (106 mg, 0.22 mmol) in dichloromethane (7 mL) at 0° C. The mixture was stirred at 0° C. for 5 minutes, then allowed to warm to room temperature and stirred for a further 5 hours. The mixture was diluted with water (15 mL) and extracted with ethyl acetate (3×20 mL). The combined ethyl acetate extracts were dried over sodium sulfate, filtered and concentrated to afford a yellow oil. Purification via silica gel chromatography (Gradient: 0% to 90% ethyl acetate in heptane) afforded the product as a white solid. By 1H NMR analysis, this was isolated as a single diastereomer. Yield: 30.1 mg, 28%. LCMS m/z 487.2 [M+H+]. 1H NMR (400 MHz, CDCl3) δ 8.24 (br d, 7.0 Hz, 2H), 7.37-7.53 (m, 4H), 6.85-6.95 (m, 2H), 4.15 (d, J=12.1 Hz, 1H), 3.90 (ap. q, J=6.8 Hz, 1H), 3.79 (d, J=12.1 Hz, 1H), 3.53 (ddd, J=10.1, 6.6, 3.3 Hz, 1H), 3.10-3.15 (m, 1H), 3.01 (dd, J=12.8, 4.2 Hz, 1H), 2.66 (dd, J=12.7, 2.7 Hz, 1H), 2.03-2.12 (m, 1H), 1.86-1.99 (m, 3H), 1.68-1.78 (m, 2H), 1.27 (s, 3H), 1.22 (s, 3H).

1. temperatureto warm to room temperature
2. stirringstirred for a further 5 hours
3. extractionextracted with ethyl acetate (3×20 mL)
4. dry with materialThe combined ethyl acetate extracts were dried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated
7. customto afford a yellow oil
8. customPurification via silica gel chromatography (Gradient: 0% to 90% ethyl acetate in heptane)