Benzene → 1-(4-Bromo-2-fluorophenyl)-3-chloro-1-propanone

To a suspension of 4-bromo-2-fluoro-benzoic acid (10 g, 45.65 mmol) in benzene (50 ml) was added thionyl chloride (7.8 ml, 12.79 g, 91.32 mmol) and the resulting mixture was heated to reflux for 12 hours. Thionyl chloride was evaporated, the reaction mixture was diluted with 1,2-dichloroethane (50 ml) and added to a slurry of aluminum chloride (5.7 g, 42.53 mmol) in 1,2 dichloroethane (50 ml) at room temperature. Ethylene was bubbled through the reaction mixture for 5 hours and the reaction mixture was stirred for another 2 hours at room temperature. It was then quenched with 2N HCl (50 ml). The layers were separated. The aqueous phase was extracted twice with 100 ml dichloromethane. The combined organic phases were washed with saturated sodium bicarbonate solution (50 ml) followed by water (50 ml). It was then dried over Na2SO4 and evaporated under reduced pressure to get the crude product, which was purified subsequently by column chromatography (silica gel, 0-5% ethyl acetate/hexane) to afford 8.6 g (71%) of the title compound as reddish solid.

1. temperaturethe resulting mixture was heated
2. temperatureto reflux for 12 hours
3. customThionyl chloride was evaporated
4. additionthe reaction mixture was diluted with 1,2-dichloroethane (50 ml)
5. customEthylene was bubbled through the reaction mixture for 5 hours
6. customIt was then quenched with 2N HCl (50 ml)
7. customThe layers were separated
8. extractionThe aqueous phase was extracted twice with 100 ml dichloromethane
9. washThe combined organic phases were washed with saturated sodium bicarbonate solution (50 ml)
10. dry with materialIt was then dried over Na2SO4
11. customevaporated under reduced pressure
12. customto get the crude product, which
13. customwas purified subsequently by column chromatography (silica gel, 0-5% ethyl acetate/hexane)

ORD record

ord-c17397325232498f9883f850f6a0839c

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08592426B2