Dimethylformamide → 4-Bromo-2-fluorobenzaldehyde

Temperature

0 °C

n-Butylmagnesium chloride (3.49 mmol) in 2.05M tetrahydrofuran solution (1.70 mL) was added to ice-cooled n-butyllithium (8.06 mmol) in 1.45M hexane (4.85 mL). The mixture was stirred at 0° C. for 15 minutes to give a suspension. To the suspension was added dropwise a toluene solution (25 mL) containing ice-cooled 1,4-dibromo-2-fluorobenzene (2.54 g, 10.0 mmol) over a period of 10 minutes, while keeping the temperature below 5° C. The resultant yellowish suspension was stirred at 0° C. for one hour, and N,N-dimethylformamide (1.0 mL, 13 mmol) was added thereto. The mixture was stirred at 0° C. for 30 minutes, and 1M aqueous acetic acid solution (15 mL) was added. The reaction mixture was extracted twice with ethyl acetate (15 mL). The organic extracts were combined, and 20% aqueous sodium hydrogen sulfite solution (5 mL) was added at room temperature. The mixture was stirred vigorously at room temperature for one hour. The aqueous phase was separated, washed with ethyl acetate (15 mL), adjusted to pH 10 with 6N sodium hydroxide solution, and extracted twice with ethyl acetate (25 ml). The organic extracts were combined, washed successively with aqueous ammonium chloride saturated solution (10 mL) and saturated aqueous sodium chloride (10 mL), dried over magnesium sulfate, and concentrated to dryness under reduced pressure to give the title compound (1.666 g, 82% yield) as an almost colorless crystalline solid.

1. customto give a suspension
2. additioncontaining ice-
3. customthe temperature below 5° C
4. stirringThe resultant yellowish suspension was stirred at 0° C. for one hour
5. stirringThe mixture was stirred at 0° C. for 30 minutes
6. extractionThe reaction mixture was extracted twice with ethyl acetate (15 mL)
7. addition20% aqueous sodium hydrogen sulfite solution (5 mL) was added at room temperature
8. stirringThe mixture was stirred vigorously at room temperature for one hour
9. customThe aqueous phase was separated
10. washwashed with ethyl acetate (15 mL)
11. extractionextracted twice with ethyl acetate (25 ml)
12. washwashed successively with aqueous ammonium chloride saturated solution (10 mL) and saturated aqueous sodium chloride (10 mL)
13. dry with materialdried over magnesium sulfate
14. concentrationconcentrated to dryness under reduced pressure

ORD record

ord-705407709885460284c295e986aab5b0

Source dataset

uspto-grants-2005_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06946559B2