Dimethylformamide → 3-Bromo-2-fluoro-4-iodobenzaldehyde

Temperature

-78 °C

To a cooled (−78° C.) solution of 2-bromo-1-fluoro-3-iodo-benzene (10.5 g, 35 mmol) in THF (100 mL) under nitrogen was added LDA (2.0 M, 21 mL, 42 mmol). The mixture was stirred for 1 h at −78° C. and then DMF (4.0 mL, 52 mmol) was added slowly. The reaction mixture was stirred for a further 1 h and then saturated aqueous ammonium chloride (50 mL) was added slowly and the mixture was warmed to RT. The layers were separated and the aqueous layer was extracted with ethyl acetate (2×60 mL). The combined organic fractions were washed with brine (100 mL), dried over anhydrous sodium sulfate, and concentrated. Purification of the residue by flash chromatography (5% ethyl acetate:hexanes) afforded 2.3 g (20%) of the title compound. 1H NMR (300 MHz, CDCl3): δ 7.43 (dd, J=9.0, 6.6 Hz, 1H), 7.69 (dd, J=9.0, 1.5 Hz, 1H), 10.08 (d, J=0.9 Hz, 1H); 19F NMR (282 MHz, CDCl3): δ−109.18 (d, J=7.3 Hz, 1F).

1. stirringThe reaction mixture was stirred for a further 1 h
2. temperaturethe mixture was warmed to RT
3. customThe layers were separated
4. extractionthe aqueous layer was extracted with ethyl acetate (2×60 mL)
5. washThe combined organic fractions were washed with brine (100 mL)
6. dry with materialdried over anhydrous sodium sulfate
7. concentrationconcentrated
8. customPurification of the residue by flash chromatography (5% ethyl acetate:hexanes)

ORD record

ord-4ea3df366c394086a942ee4a46c8a830

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08378104B2