反应详情

A 25-mL round bottom flask containing a magnetic stir bar and fitted with an inert gas inlet was charged with ethyl 1-(4-chloro-3-methoxyphenyl)piperidine-4-carboxylate, hydrochloride salt (367 mg, 1.23 mmol), AcOH (6 mL) and water (3.0 mL). The mixture was treated with N-chlorosuccinimide (206 mg, 1.54 mmol) in one portion. The mixture was stirred under argon at RT overnight and then diluted with water (20 mL) and Et2O (60 mL). The pH of the mixture was adjusted to a pH=10. The phases were separated and the aqueous phase was extracted with Et2O. The combined Et2O extracts were washed with brine, dried (MgSO4) and concentrated on a rotary evaporator. The resultant residue was purified by flash chromatography using a 12 g silica gel cartridge and gradient elution from 50:1 Hex/EtOAc to 20:1 Hex/EtOAc to elute the product. The fractions containing the product were pooled and concentrated on a rotary evaporator to give ethyl 1-(2,4-dichloro-5-methoxyphenyl)piperidine-4-carboxylate (255 mg, 0.77 mmol, 70% yield) as a clear oil, which solidified on standing at room temperature. 1H-NMR (400 MHz, CDCl3) δ ppm 7.33 (1 H, s), 6.58 (1 H, s), 4.15 (2 H, qd, J=7.04, 6.87 Hz), 3.87 (3 H, s), 3.33 (2 H, d, J=11.70 Hz), 2.70 (2 H, t, J=9.66 Hz), 2.43 (1 H, dq, J=10.17, 5.09 Hz), 1.94-2.05 (4 H, m), 1.22-1.30 (3 H, m).

1. additionA 25-mL round bottom flask containing a magnetic stir bar
2. customfitted with an inert gas inlet
3. customThe phases were separated
4. extractionthe aqueous phase was extracted with Et2O
5. washThe combined Et2O extracts were washed with brine
6. dry with materialdried (MgSO4)
7. concentrationconcentrated on a rotary evaporator
8. customThe resultant residue was purified by flash chromatography
9. washa 12 g silica gel cartridge and gradient elution from 50:1 Hex/EtOAc to 20:1 Hex/EtOAc
10. washto elute the product
11. additionThe fractions containing the product
12. concentrationconcentrated on a rotary evaporator