Dimethylformamide → 2,3-Difluoro-6-methoxybenzaldehyde

Temperature

-78 °C

To a solution of diisopropylamine (14.6 mL, 103.5 mmol) in dry THF (50 mL) cooled to −78° C. was added a solution of BuLi (1.6 M in hexane, 47 mL, 75.9 mmol) dropwise under argon, keeping the temperature below −60° C. It was stirred at this temperature for 15 minutes after which a solution of 1,2-difluoro-4-(methyloxy)benzene (10 g, 69 mmol) in dry THF (50 mL) was added slowly. The mixture was left stirring at −78° C. for 45 minutes followed by slow addition of DMF (6.37 mL, 82.8 mmol) maintaining the temperature below −60° C. The resulting mixture was stirred at −78° C. for circa 3.5 hours after which water (100 mL) was added and the cooling removed to allow it to warm up to room temperature. It was diluted with EtOAc and the organic separated. The aqueous was re-extracted with EtOAc (3×) and the combined organics washed with brine and dried over MgSO4. The crude material (10.26 g) was purified by flash chromatography to afford the title compound (D25) (9 g).

1. customthe temperature below −60° C
2. additionwas added slowly
3. waitThe mixture was left
4. temperaturemaintaining the temperature below −60° C
5. additionwas added
6. customthe cooling removed
7. temperatureto warm up to room temperature
8. additionIt was diluted with EtOAc
9. extractionThe aqueous was re-extracted with EtOAc (3×)
10. washthe combined organics washed with brine
11. dry with materialdried over MgSO4
12. customThe crude material (10.26 g) was purified by flash chromatography

ORD record

ord-0c8eecbd727c4aa3b3857964827a4d34

Source dataset

uspto-grants-2011_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07960563B2