Hydrochloric Acid → 1-(2-Bromo-4-chlorophenyl)-2,2,2-trifluoroethanone

2-Bromo-4-chloro-benzoic acid methyl ester (12.4 g, 50 mmol) in toluene (200 ml) was cooled to −70° C., and trifluoromethyl trimethyl silane (13 ml, 70 mmol) was added. Tetrabutylamonium fluoride (1M, 2.5 ml) was added dropwise, and the mixture was allowed to warm to room temperature over 4 h, after which it was stirred for 10 h at room temperature. The reaction mixture was concentrated to give the crude [1-(2-bromo-4-chloro-phenyl)-2,2,2-trifluoro-1-methoxy-ethoxy]-rimethyl-silane. The crude intermediate was dissolved in methanol (100 ml) and 6N HCl (100 ml) was added. The mixture was kept at 45-50° C. for 12 h. Methanol was removed, and the crude was extracted with dichloromethane (200 ml). The combined DCM layer was washed with water (50 ml), NaHCO3 (50 ml), brine (50 ml), and dried over sodium sulfate. Removal of solvent gave a crude product, which was purified by ISCO column chromatography, using 1-2% ethyl acetate in hexane as solvent, to afford 1-(2-bromo-4-chloro-phenyl)-2,2,2-trifluoro-ethanone (10 g, 70%). 1H-NMR (300 MHz, CDCl3): δ (ppm) 7.50 (d,1H), 7.65(d,1H), 7.80(s,1H).

1. concentrationThe reaction mixture was concentrated
2. customto give the crude [1-(2-bromo-4-chloro-phenyl)-2,2,2-trifluoro-1-methoxy-ethoxy]-rimethyl-silane
3. waitThe mixture was kept at 45-50° C. for 12 h
4. customMethanol was removed
5. extractionthe crude was extracted with dichloromethane (200 ml)
6. washThe combined DCM layer was washed with water (50 ml), NaHCO3 (50 ml), brine (50 ml)
7. dry with materialdried over sodium sulfate
8. customRemoval of solvent
9. customgave a crude product, which
10. customwas purified by ISCO column chromatography

ORD record

ord-4e3cdf2606b6422ea0a9ba0a2c806d20

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08772482B2