反应详情

温度

-78 °C

To tert-butyl 4-(2-ethoxy-2-oxoethyl)-4-hydroxypiperidine-1-carboxylate (12 g) in DCM (60 ml) at −78° C. under nitrogen was added by syringe diethylaminosulfur trifluoride (DAST) (8.3 ml). The mixture was stirred at −78° C. for 3 hours, then slowly warming up to rt, the mixture was then poured to aqueous sodium bicarbonate (200 ml), extracted with ethyl acetate (200 ml+100 ml), organic layer dried over sodium sulphate, solvent removed under vacuum. The oily residue was taken into ethanol (150 ml) and water (150 ml). Magnesium sulphate (5.4 g) was then added, followed by potassium permanganate (7.2 g). The mixture was stirred at rt for 1 hour, then extracted with ethyl acetate (600 ml). Organic layer was washed with brine (150 ml), dried over sodium sulphate, solvent removed under vacuum, residue was columned on silica gel using heptane:EtOAc (7:1) as eluant to give tert-butyl 4-(2-ethoxy-2-oxoethyl)-4-fluoropiperidine-1-carboxylate (3.8 g) as a colourless oil. 1H NMR (CDCl3) δ: 4.16 (q, 2H), 3.95 (br, 2H), 3.10 (t, br, 2H), 2.64 (d, 2H), 1.93 (t, br, 2H), 1.6-1.85 (m, 2H), 1.46 (s, 9H), 1.27 (t, 3H).

1. temperatureslowly warming up to rt
2. extractionextracted with ethyl acetate (200 ml+100 ml), organic layer
3. dry with materialdried over sodium sulphate, solvent
4. customremoved under vacuum
5. additionMagnesium sulphate (5.4 g) was then added
6. stirringThe mixture was stirred at rt for 1 hour
7. extractionextracted with ethyl acetate (600 ml)
8. washOrganic layer was washed with brine (150 ml)
9. dry with materialdried over sodium sulphate, solvent
10. customremoved under vacuum, residue