Sulfuric Acid → 1-(4-Fluorophenyl)-3-methyl-1-butanone

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)

ORD record

ord-24888662d0a648df97902b1a24c5e89e

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09150582B2