Reaction #1563929

Reaction equation

4-chloro-N-methoxy-N-methylbutanamide

2-Bromo-1,4-difluorobenzene

isopropyl magnesium chloride

→

title compound

Yield 66.3%

4-chloro-1-(2,5-difluorophenyl)butan-1-one

Yield 66.3%

Solvents

THF

THF

Conditions

Workup

1. 1
   OtherThe reaction mixture thus obtained
2. 2
   TemperatureThe reaction mixture was cooled again to −50° C
3. 3
   workup.STIRRINGwith stirring
4. 4
   workup.WAITthe stirring was continued at 0° C. for 1 h
5. 5
   OtherThe reaction mixture was quenched with saturated aqueous NH4Cl solution
6. 6
   Extractionextracted with ethylacetate
7. 7
   OtherThe organic layer collected
8. 8
   Washwas washed with water (500 mL)
9. 9
   Dryingwith brine solution, dried over anhydrous sodium sulfate
10. 10
    Concentrationconcentrated under reduced pressure
11. 11
    Otherto afford a crude liquid residue
12. 12
    OtherThe residue thus obtained
13. 13
    Otherwas purified by column chromatography (using 60-120 silica gel and 5% EtOAc in Hexane as eluent)

Procedure

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.

Source