反应详情

温度

65 °C

A mixture of Example 476F (11.4 g, 23.6 mmol), LiOH.H2O (2.97 g, 70.8 mmol), methanol (200 mL), THF (100 mL) and water (10 mL) was heated at 65° C. for 4.25 hours. When hydrolysis was complete, triethylamine (65.8 mL, 472 mmol) was added, followed by SnCl2.2H2O (26.6 g, 118 mmol). The mixture was heated at 65° C. overnight, then cooled to room temperature when hydrogenation was complete. DMF (200 mL), triethylamine (16.5 mL, 118 mmol) and HATU (17.95 g, 47.2 mmol) were added and the mixture was stirred overnight, filtered through diatomaceous earth (Celite®), concentrated under vacuum, diluted with ethyl acetate, washed with water and brine, dried (MgSO4), filtered, and concentrated under vacuum. Hexane was added to a solution of the concentrate in diethyl ether to invoke formation of a solid which was filtered, rinsed with hexane, and dried under vacuum to give 8.8 g (89%) of the desired product. MS (ESI) m/e 421 (M+H)+; 1H NMR (300 MHz, DMSO-d6) □ 9.69 (s, 1H), 7.81 (s, 1H), 7.65 (d, J=8.5 Hz, 1H), 7.04 (d, J=2.0 Hz, 1H), 6.91 (dd, J=2.0, 8.5 Hz, 1H), 6.76 (s, 1H), 6.65 (s, 1H), 5.11 (s, 2H), 3.67 (s, 3H), 3.65-3.72 (m, 2H), 0.86-0.94 (m, 2H), -0.03 (s, 9H).

1. customWhen hydrolysis
2. temperaturecooled to room temperature when hydrogenation
3. filtrationfiltered through diatomaceous earth (Celite®)
4. concentrationconcentrated under vacuum
5. additiondiluted with ethyl acetate
6. washwashed with water and brine
7. dry with materialdried (MgSO4)
8. filtrationfiltered
9. concentrationconcentrated under vacuum
10. additionHexane was added to a solution of the
11. concentrationconcentrate in diethyl ether
12. filtrationwas filtered
13. washrinsed with hexane
14. customdried under vacuum