反应详情

To a stirring solution of the ketone from step 1 (250 g, 1.05 mol) and triethylamine (223 g, 2.20 mol) in toluene (4.2 liter) at 0° C. is slowly added trimethylsilyl trifluoromethanesulfonate (TMS-OTf, 280 g, 1.26 mol) via addition funnel. The stirring is continued for 30 min and the mixture allowed to warm to ambient temperature. Water (5 liter) is added and the aqueous layer extracted with EtOAc (3×500 ml). The organics are combined, dried over MgSO4 and the solvent removed in vacuo. Hexane (4×500 ml) is added and the solvent removed in vacuo. At the fourth co-distillation, a slurry formed (˜300 ml). The mixture is cooled to 0° C. and solids filtered. The filtrated is concentrated to a slurry, cooled and filtered (2nd crop). Solids are combined to result in 273.7 g (84%) title compound as a yellow solid. 1H NMR (CDCl3) δ 0.21 (s, 9 H), 2.20 (brs, 2 H), 3.52 (brs, 2 H), 3.62 (brs, 2 H), 4.89 (brs, 1 H), 6.65 (t, J=8 Hz, 1 H), 7.67 (d, J=12 Hz, 1 H), 7.73 (d, J=12 Hz, 1 H. Anal. Calcd for C14H19FN2O3Si: C, 54.17; H, 6.17; N, 9.02. Found: C, 54.01; H, 6.29; N, 9.15.

1. customat 0° C.
2. additionvia addition funnel
3. extractionthe aqueous layer extracted with EtOAc (3×500 ml)
4. dry with materialdried over MgSO4
5. customthe solvent removed in vacuo
6. additionHexane (4×500 ml) is added
7. customthe solvent removed in vacuo
8. customAt the fourth co-distillation, a slurry formed (˜300 ml)
9. temperatureThe mixture is cooled to 0° C.
10. filtrationsolids filtered
11. concentrationThe filtrated is concentrated to a slurry
12. temperaturecooled
13. filtrationfiltered (2nd crop)