Реакция #1563929

Уравнение реакции

4-chloro-N-methoxy-N-methylbutanamide

2-Bromo-1,4-difluorobenzene

isopropyl magnesium chloride

→

title compound

Выход 66.3%

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

Выход 66.3%

Растворители

THF

THF

Условия реакции

Обработка

1. 1
   ДругоеThe reaction mixture thus obtained
2. 2
   ТемператураThe 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
   ДругоеThe reaction mixture was quenched with saturated aqueous NH4Cl solution
6. 6
   Экстракцияextracted with ethylacetate
7. 7
   ДругоеThe organic layer collected
8. 8
   Промывкаwas washed with water (500 mL)
9. 9
   Сушкаwith brine solution, dried over anhydrous sodium sulfate
10. 10
    Концентрированиеconcentrated under reduced pressure
11. 11
    Другоеto afford a crude liquid residue
12. 12
    ДругоеThe residue thus obtained
13. 13
    Другоеwas purified by column chromatography (using 60-120 silica gel and 5% EtOAc in Hexane as eluent)

Методика

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.

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