反应详情

Lithium borohydride (0.44 g, 20 mmol) was added to a solution of 1-(1,1-dimethylethyl) 4-ethyl 4-(2-methyl-2-propenyl)-1,4-piperidinedicarboxylate (Description 89, 3.11 g, 10 mmol) in tetrahydrofuran and the mixture was stirred under reflux for 18 hours. The mixture was cooled, toluene (20 mL) and lithium borohydride (0.44 g, 20 mmol) were added and the mixture was stirred under reflux for 6 hours. The mixture was cooled and saturated aqueous ammonium chloride (20 mL) and water (50 mL) were added. The mixture was extracted with ethyl acetate (3×500 mL) and the combined organic fractions were washed with aqueous citric acid (10%, 50 mL), saturated aqueous sodium hydrogen carbonate (50 mL) and brine (50 mL), dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with isohexane/EtOAc (70:30) to give the title compound as a colorless foam (1.81 g, 67%). 1H NMR (400 MHz, CDCl3) shows two slowly equilibrating tautomers; major: δ 4.92 (1H, s), 4.77 (1H, s), 3.86–3.20 (10H, m), 2.14 (2H, s), 1.82 (3H, s), and 1.46 (9H, s); minor; δ 4.87 (1H, s), 4.66 (1H, s), 3.86–3.20 (10H, m), 2.11 (2H, s), 1.76 (3H, s), and 1.46 (9H, s). m/z (ES+) 270 (M+1).

1. temperatureunder reflux for 18 hours
2. temperatureThe mixture was cooled
3. stirringthe mixture was stirred
4. temperatureunder reflux for 6 hours
5. temperatureThe mixture was cooled
6. extractionThe mixture was extracted with ethyl acetate (3×500 mL)
7. washthe combined organic fractions were washed with aqueous citric acid (10%, 50 mL), saturated aqueous sodium hydrogen carbonate (50 mL) and brine (50 mL)
8. dry with materialdried (MgSO4)
9. customthe solvent was evaporated under reduced pressure
10. customThe residue was purified by flash column chromatography on silica gel
11. washeluting with isohexane/EtOAc (70:30)