反应详情

To a solution of 4-fluoro-benzonitrile (6 g, 49.5 mmol) in diethyl ether (200 mL) was added i-BuMgCl (1 M soln in THF) and the reaction mixture heated to reflux for 16 hours. The reaction mixture was cooled to room temperature and poured into a mixture 6 N H2SO4 (60 mL) and ice (500 mL), then stirred at 0° C. for 30 min. The aqueous layer was extracted with ethyl acetate (200 mL), the combined organic layers were washed with brine (100 mL), dried (MgSO4), and concentrated. The residue was purified by column chromatography (80 g, SiO2, 0 to 40% diethyl ether/dichloromethane 1:1 in hexanes) to provide 1-(4-fluorophenyl)-3-methylbutan-1-one as a colorless oil (3.72 g, 42%): 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.00 (d, J=6.78 Hz, 6H), 2.29 (dt, J=13.47, 6.64 Hz, 1H), 2.81 (d, J=6.78 Hz, 2H), 7.06-7.19 (m, 2H), 7.94-8.02 (m, 2H); MS m/z 172 (Dimer-OH)++.

1. temperaturethe reaction mixture heated
2. temperatureto reflux for 16 hours
3. extractionThe aqueous layer was extracted with ethyl acetate (200 mL)
4. washthe combined organic layers were washed with brine (100 mL)
5. dry with materialdried (MgSO4)
6. concentrationconcentrated
7. customThe residue was purified by column chromatography (80 g, SiO2, 0 to 40% diethyl ether/dichloromethane 1:1 in hexanes)