Dimethylformamide → 2,4-Difluoro-3-methylbenzaldehyde

Temperature

-78 °C

A cooled (−78° C.) solution of 2,4-difluoro-3-methylbromobenzene (2.000 g; 9.661 mmol) in anhydrous THF (36 ml) was treated dropwise (over 10 min.) with a solution of 1.6M n-BuLi in hexanes (6.04 ml; 9.661 mmol) while maintaining the temperature below −70° C. This mixture was further stirred at −78° C. for 2 min. before anhydrous DMF (1.49 ml; 19.326 mmol) was added dropwise (over 10 min.) while maintaining the temperature below −70° C. After completion of the addition, the resulting light brown solution was further stirred at −78° C. for 1 h30. The resulting mixture was then quenched at −78° C. with aq. sat. NH4Cl (10 ml), and was then allowed to warm-up to rt. Ether (50 ml) and water (20 ml) were added, and the organic layer was dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure (caution: rotary evaporation bath at 30° C. because the aldehyde is volatile). The crude was purified by FC (DCM) to give the pure product 2,4-difluoro-3-methyl-benzaldehyde as a pale yellow oil (1.250 g; 83%).

1. temperaturewhile maintaining the temperature below −70° C
2. additionwas added dropwise (over 10 min.)
3. temperaturewhile maintaining the temperature below −70° C
4. additionAfter completion of the addition
5. customThe resulting mixture was then quenched at −78° C. with aq. sat. NH4Cl (10 ml)
6. temperatureto warm-up to rt
7. additionEther (50 ml) and water (20 ml) were added
8. dry with materialthe organic layer was dried over anh. MgSO4
9. filtrationfiltered
10. concentrationconcentrated to dryness under reduced pressure (caution
11. customrotary evaporation bath at 30° C. because the aldehyde is volatile
12. customThe crude was purified by FC (DCM)

ORD record

ord-d6f79cf7fdbe4f20b6a3b85d4d3e20c6

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08188082B2