Dimethylformamide → 2-bromo-6-chloro-3-fluorobenzaldehyde

To a −78° C. solution of 2-Bromo-4-chloro-1-fluoro-benzene (2.90 g, 13.9 mmol) in 30 mL tetrahydrofuran under an atmosphere of nitrogen was added lithium diisopropylamide solution (1.8M in tetrahydrofuran/heptane/ethylbenzene, 10.0 mL, 18.0 mmol) at such a rate that the internal reaction temperature did not exceed −69° C. After 1 hour at −78° C., dimethylformamide (1.39 mL, 18.0 mmol) was added at such a rate that the internal temperature did not exceed −69° C. After 30 minutes at −78° C., the reaction was quenched with saturated aqueous ammonium hydroxide solution. The resulting mixture was extracted with diethyl ether. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, concentrated in vacuo, and purified by flash chromatography (gradient elution with 0 to 5% ethylacetate/hexanes) to yield 2-Bromo-6-chloro-3-fluoro-benzaldehyde (440 mg, 1.85 mmol). MS (ESI) 236.9 (M+H)+.

1. customdid not exceed −69° C
2. customdid not exceed −69° C
3. waitAfter 30 minutes at −78° C.
4. customthe reaction was quenched with saturated aqueous ammonium hydroxide solution
5. extractionThe resulting mixture was extracted with diethyl ether
6. washThe organic layer was washed with brine
7. dry with materialdried over anhydrous magnesium sulfate
8. concentrationconcentrated in vacuo
9. custompurified by flash chromatography (gradient elution with 0 to 5% ethylacetate/hexanes)

ORD record

ord-296093b6d5634e5ca8f974f46d89cf7d

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08299077B2