2-Bromo-1,4-difluorobenzene → 4-Chloro-1-(2,5-difluorophenyl)butan-1-one

Temperature

0 °C

2-Bromo-1,4-difluorobenzene (53.6 g, 277.74 mmol) in THF cooled to −50° C. was added to isopropyl magnesium chloride (2M in THF)(133 mL, 266 mmol). The reaction mixture thus obtained was warmed to 0° C. and stirred for 1 h. The reaction mixture was cooled again to −50° C. 4-chloro-N-methoxy-N-methylbutanamide (40 g, 241.52 mmol) in THF (200 mL) was added dropwise to this reaction mixture with stirring and the stirring was continued at 0° C. for 1 h. The reaction mixture was quenched with saturated aqueous NH4Cl solution, extracted with ethylacetate. The organic layer collected was washed with water (500 mL) and then with brine solution, dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford a crude liquid residue. The residue thus obtained was purified by column chromatography (using 60-120 silica gel and 5% EtOAc in Hexane as eluent) to afford 35 g of the title compound as a colourless liquid.

1. customThe reaction mixture thus obtained
2. temperatureThe reaction mixture was cooled again to −50° C
3. stirringwith stirring
4. waitthe stirring was continued at 0° C. for 1 h
5. customThe reaction mixture was quenched with saturated aqueous NH4Cl solution
6. extractionextracted with ethylacetate
7. customThe organic layer collected
8. washwas washed with water (500 mL)
9. dry with materialwith brine solution, dried over anhydrous sodium sulfate
10. concentrationconcentrated under reduced pressure
11. customto afford a crude liquid residue
12. customThe residue thus obtained
13. customwas purified by column chromatography (using 60-120 silica gel and 5% EtOAc in Hexane as eluent)

ORD record

ord-bfaf522b87e34ac2b7c5dc6751b30e23

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09045479B2