反应详情

A 100-mL 3-neck round-bottom flask was charged with anhydrous THF (20 mL) and 60% dispersion sodium hydride (0.574 g, 14.35 mmol) and placed under nitrogen atmosphere. At ambient temperature, ethyl 2-(diethoxyphosphoryl)propanoate (3.42 g, 14.35 mmol) was added to the suspension via syringe over a period of 5 min and the mixture stirred for 30 min. The resulting clear mixture was treated with a solution of tert-butyl 4-oxopiperidine-1-carboxylate (2.2 g, 11.04 mmol) in anhydrous THF (5 mL) and the reaction continued at ambient temperature for 1 h. At the conclusion of this period, the mixture was quenched with saturated NH4Cl solution and the mixture was then extracted with EtOAc (3×50 mL). The extract was washed with brine, dried (MgSO4) and concentrated to give the crude product. The crude product was purified by flash chromatography using an 80 g silica gel gradient elution from 20:1 Hex/EtOAc to 6:1 Hex/EtOAc. The fractions containing the product were pooled and concentrated on a rotary evaporator to give tert-butyl 4-(1-ethoxy-1-oxopropan-2-ylidene)piperidine-1-carboxylate as a colorless liquid. 1H-NMR (500 MHz, CDCl3) δ ppm 4.18 (2 H, q, J=7.15 Hz), 3.43 (4 H, dt, J=23.71, 5.88 Hz), 2.61 (2 H, t, J=5.77 Hz), 2.33 (2 H, t, J=5.77 Hz), 1.86 (3 H, s), 1.45 (9H, s), 1.26-1.31 (3H, m, J=7.15 Hz).

1. waitthe reaction continued at ambient temperature for 1 h
2. customAt the conclusion of this period, the mixture was quenched with saturated NH4Cl solution
3. extractionthe mixture was then extracted with EtOAc (3×50 mL)
4. washThe extract was washed with brine
5. dry with materialdried (MgSO4)
6. concentrationconcentrated
7. customto give the crude product
8. customThe crude product was purified by flash chromatography
9. washan 80 g silica gel gradient elution from 20:1 Hex/EtOAc to 6:1 Hex/EtOAc
10. additionThe fractions containing the product
11. concentrationconcentrated on a rotary evaporator