反应详情

温度

81.5 °C

A 22-L four-neck round bottom flask equipped with mechanical stirrer, heating mantel, temperature probe, nitrogen inlet, and a reflux condenser with nitrogen outlet was purged with nitrogen for 30 min before use. The product of Step C (603.5 g, 1.46 mol, 1 eq), AIBN (241 g, 1.46 mol, 1 eq), tris(trimethylsilyl)silane (910 mL, 2.93 mol, 2 eq) and toluene (16.3 L) were added and the suspension was degassed with nitrogen purge through the suspension for 20 min. The reaction was heated to 80-83° C. for 1 h after which time the heat was shut off, and the reaction cooled to rt over 12-18 h. TLC showed the reaction was complete. The reaction was poured directly into a BIOTAGE dry 5-kg column that was eluted with 16 L of 50% EtOAc in heptane, followed by 32 L of EtOAc and provided the product of Step D of a golden thick oil, which slowly crystallized on standing. 1H NMR (CHLOROFORM-d) δ: 4.64 (brd. s, 1H), 4.07-4.25 (m, 2H), 3.89 (ddd, J=8.8, 7.2, 4.5 Hz, 1H), 3.53-3.67 (m, 3H), 2.17 (dd, J=13.3, 6.2 Hz, 1H), 1.98-2.06 (m, 1H), 1.86-1.97 (m, 1H), 1.68-1.81 (m, 2H), 1.46-1.56 (m, 2H), 1.44 (s, 9H). Calculated for C13H23NO4: 202.2 (M−55). found: 202.2.

1. customA 22-L four-neck round bottom flask equipped with mechanical stirrer
2. temperatureheating mantel, temperature probe, nitrogen inlet, and a reflux condenser with nitrogen outlet
3. customwas purged with nitrogen for 30 min before use
4. customthe suspension was degassed with nitrogen
5. custompurge through the suspension for 20 min
6. temperaturethe reaction cooled to rt over 12-18 h
7. additionThe reaction was poured directly into a BIOTAGE
8. customdry 5-kg column that
9. washwas eluted with 16 L of 50% EtOAc in heptane