反应详情

温度

-78 °C

To a solution of 4-diisopropylamidopyridine (3.2 g, 15.54 mmol) in anhydrous diethyl ether (160 mL) at −78° C. was added a 1M solution of LDA in diethyl ether (23.27 mL) and the reaction mixture stirred at −78° C. for 2 hours. A solution of 1-(4-fluorophenyl)-3-methylbutan-1-one (3.5 g, 19.42 mmol) in anhydrous diethyl ether (5 mL) was added dropwise, and the reaction was stirred at −78° C. for 30 min. The reaction mixture was quenched with brine (100 mL), extracted with ethyl acetate (3×50 mL), dried (MgSO4), and concentrated. The crude mixture was stirred with 6 N HCl (50 mL) for 12 hours, then cooled to 0° C. Sodium hydroxyde (15 g, 37.5 mmol) was added in 3 portions, the reaction mixture was stirred at 0° C. for 30 min, then extracted with ethyl acetate (3×100 mL). The organic layers were dried (MgSO4), concentrated and purified by column chromatography (40 g, SiO2, 0 to 40% ethyl acetate in hexanes) to provide 3-(4-fluorophenyl)-3-isobutylfuro[3,4-c]pyridin-1(3H)-one (296 mg, 7%) as an off-white solid. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.80-0.91 (m, 6H), 1.54-1.66 (m, 1H), 2.06 (dd, J=14.88, 6.97 Hz, 1H), 2.48 (dd, J=15.07, 5.27 Hz, 1H), 7.04-7.14 (m, 2H), 7.46-7.56 (m, 2H), 7.77 (dd, J=5.09, 0.94 Hz, 1H), 8.85 (d, J=4.90 Hz, 1H), 9.01 (s, 1H); MS m/z 286 (M+H)+.

1. stirringthe reaction was stirred at −78° C. for 30 min
2. customThe reaction mixture was quenched with brine (100 mL)
3. extractionextracted with ethyl acetate (3×50 mL)
4. dry with materialdried (MgSO4)
5. concentrationconcentrated
6. stirringThe crude mixture was stirred with 6 N HCl (50 mL) for 12 hours
7. temperaturecooled to 0° C
8. additionSodium hydroxyde (15 g, 37.5 mmol) was added in 3 portions
9. stirringthe reaction mixture was stirred at 0° C. for 30 min
10. extractionextracted with ethyl acetate (3×100 mL)
11. dry with materialThe organic layers were dried (MgSO4)
12. concentrationconcentrated
13. custompurified by column chromatography (40 g, SiO2, 0 to 40% ethyl acetate in hexanes)