反应详情

温度

80 °C

To a stirring solution of 4-piperidone monohydrate hydrochloride (258.7 g, 1.68 mol) and diisopropylethylamine (590 ml, 3.39 mol) in acetonitrile (2.5 liter) is added 3,4-difluoronitrobenzene (186.3 ml, 1.68 mol). The mixture is heated to 80° C. and stirred overnight. The solvent is cooled to ambient temperature and removed under reduced pressure. The residue is partitioned between ethyl acetate and 10% aqueous HCl (1.20 liter each). The layers are shaken, and the organic layer is separated and washed with 10% HCl and saline (800 ml each). The organic layer is dried over MgSO4 and filtered. As the solvent is removed under reduced pressure a solid begins to precipitate out (˜¼ volume). The resulting slurry is cooled to 0–5° C. and filtered to afford 333.7 g of the title compound, 1H NMR (400 MHz, CDCl3) δ 2.65 (m, 4H), 3.65 (m, 4H), 6.98 (m, 1H), 7.26 (s, 1H), 8.00 (m, 1H).

1. temperatureThe solvent is cooled to ambient temperature
2. customremoved under reduced pressure
3. customThe residue is partitioned between ethyl acetate and 10% aqueous HCl (1.20 liter each)
4. stirringThe layers are shaken
5. customthe organic layer is separated
6. washwashed with 10% HCl and saline (800 ml each)
7. dry with materialThe organic layer is dried over MgSO4
8. filtrationfiltered
9. customAs the solvent is removed under reduced pressure a solid
10. customto precipitate out (˜¼ volume)
11. temperatureThe resulting slurry is cooled to 0–5° C.
12. filtrationfiltered