反应详情

Ethyl 4-oxocyclohexane carboxylate (10.0 g, 58.8 mmol) and pyrrolidine (5.87 g, 82.7 mmol) in toluene (100 mL) and molecular sieves (40 g of 4 Å sieves) are heated to reflux overnight using Dean Stark apparatus. The mixture is filtered and the excess pyrrolidine is removed in vacuo. The resulting mixture is diluted with toluene (50 mL) and treated with methyl iodide (8.96 g, 63.1 mmol). After heating at reflux for 15 hours, the mixture is allowed to cool to RT and silica (3 g) and water (30 mL) are added. The mixture is stirred at RT for 3 hours and partitioned between water and diethyl ether. The organic portion is separated and washed with water, brine, dried (MgSO4) and concentrated in vacuo. Purification by chromatography on silica eluting with iso-hexane:EtOAc (19:1 increasing to 9:1) affords the title compound. 1H NMR (400 MHz, DMSO-d6) δ 4.15 (2H, q), 2.89 (1H, m), 2.51 (1H, m), 2.38 (1H, m), 2.21 (3H, m), 1.89 (1H, m), 1.62 (1H, m), 1.22 (3H, t), 0.95 (3H, d).

1. temperatureto reflux overnight
2. filtrationThe mixture is filtered
3. customthe excess pyrrolidine is removed in vacuo
4. additionThe resulting mixture is diluted with toluene (50 mL)
5. temperatureAfter heating
6. temperatureat reflux for 15 hours
7. custompartitioned between water and diethyl ether
8. customThe organic portion is separated
9. washwashed with water, brine
10. dry with materialdried (MgSO4)
11. concentrationconcentrated in vacuo
12. customPurification by chromatography on silica eluting with iso-hexane:EtOAc (19:1 increasing to 9:1)