Phenylacetic Acid → 1-(5-Fluoro-2-hydroxyphenyl)-2-phenylethanone

Temperature

0 °C

Phenylacetic acid (8.09 g, 59.46 mmoles) was dissolved in 15 ml dichloromethane. To this mixture, oxalylchloride (5.2 ml, 59.46 mmoles) and DMF (3 drops) were added at 0° C. and stirred for 30 min. The solvent was evaporated and dissolved in 15 ml dichloromethane. To this mixture, 4-fluoroanisole (5.0 g, 39.64 mmoles) was added and cooled to 0° C. At 0° C. AlCl3 (7.92 g, 59.46 mmoles) was added and the reaction mixture was warmed to RT and stirred for 12 h. The reaction mixture was quenched by the addition of 2N HCl, extracted with ethyl acetate, dried over sodium sulphate and concentrated. The crude product was purified by column chromatography with ethyl acetate:petroleum ether to afford the title compound as off-white solid (5.1 g, 56% yield. 1H-NMR (δ ppm, DMSO-d6, 400 MHz): δ 11.43 (s, 1H), 7.77 (dd, J=9.5, 3.2 Hz, 1H), 7.42 (dt, J=8.7, 3.2 Hz, 1H), 7.33 (t, J=7.3 Hz, 2H), 7.26 (m, 3H), 7.01 (q, J=4.6 Hz, 1H), 4.42 (s, 2H).

1. customThe solvent was evaporated
2. dissolutiondissolved in 15 ml dichloromethane
3. customAt 0° C
4. temperaturethe reaction mixture was warmed to RT
5. stirringstirred for 12 h
6. customThe reaction mixture was quenched by the addition of 2N HCl
7. extractionextracted with ethyl acetate
8. dry with materialdried over sodium sulphate
9. concentrationconcentrated
10. customThe crude product was purified by column chromatography with ethyl acetate

ORD record

ord-9b92b71974b94525a8a21fcfee19b2d5

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09421209B2