反应详情

To a stirred solution of 1-(2-fluoro-4-nitrophenyl)piperidin-4-one (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 under reduced pressure. Hexane (4×500 ml) is added and the solvent removed under reduced pressure. At the fourth co-distillation, a slurry forms (−300 ml). The mixture is cooled to 0° C. and the solids filtered. The filtrate is concentrated to a slurry, cooled and filtered (2nd crop). Solids are combined to give 273.7 g (84%) of the title compound as a yellow solid, 1H NMR (CDCl3) δ 0.21 (s, 9H), 2.20 (brs, 2H), 3.52 (brs, 2H), 3.62 (brs, 2H), 4.89 (brs, 1H), 6.65 (t, 1H), 7.67 (d, 1H), 7.73 (d, 1H).

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 under reduced pressure
6. additionHexane (4×500 ml) is added
7. customthe solvent removed under reduced pressure
8. temperatureThe mixture is cooled to 0° C.
9. filtrationthe solids filtered
10. concentrationThe filtrate is concentrated to a slurry
11. temperaturecooled
12. filtrationfiltered (2nd crop)