反应详情

温度

0 °C

To a solution of 3-(4-fluorophenyl)-3-isobutylfuro[3,4-c]pyridin-1(3H)-one (296 mg, 1.04 mmol) in dichloromethane (5 mL) at 0° C. was added 1 N HCl in diethyl ether. The reaction mixture was stirred at 0° C. for 40 min., then filtered and the precipitated hydrochloride salt dried in high vacuo for 1 hour. The precipitate was re-dissolved in ethanol (10 mL), PtO2 (40 mg) was added, and the reaction mixture was hydrogenated at 40 psi for 30 min. The mixture was filtered through a pad of diatomaceous earth, the filtrate concentrated in vacuo. The residue was re-dissolved in dichloromethane (50 mL) and stirred with sat. NaHCO3 soln. for 20 min., then dried (MgSO4) and concentrated. The residue was purified by column chromatography (4 g, SiO2, 0 to 2.5% methanol in dichloromethane) to provide 3-(4-fluorophenyl)-3-isobutyl-4,5,6,7-tetrahydrofuro[3,4-c]pyridin-1(3H)-one (160 mg, 53%): 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.83-0.98 (m, 6H), 1.56 (br. s., 1H), 1.65 (ddd, J=13.37, 6.59, 5.27 Hz, 1H), 1.72-1.81 (m, 1H), 2.15-2.38 (m, 3H), 2.84-3.05 (m, 2H), 3.34-3.50 (m, 1H), 3.58-3.73 (m, 1H), 7.00-7.12 (m, 2H), 7.27-7.34 (m, 2H); MS m/z 290 (M+H)+, 288 (M−H)−.

1. filtrationfiltered
2. dry with materialthe precipitated hydrochloride salt dried in high vacuo for 1 hour
3. dissolutionThe precipitate was re-dissolved in ethanol (10 mL)
4. additionPtO2 (40 mg) was added
5. waitthe reaction mixture was hydrogenated at 40 psi for 30 min
6. filtrationThe mixture was filtered through a pad of diatomaceous earth
7. concentrationthe filtrate concentrated in vacuo
8. dissolutionThe residue was re-dissolved in dichloromethane (50 mL)
9. stirringstirred with sat. NaHCO3 soln
10. waitfor 20 min.
11. dry with materialdried (MgSO4)
12. concentrationconcentrated
13. customThe residue was purified by column chromatography (4 g, SiO2, 0 to 2.5% methanol in dichloromethane)