Dimethylformamide → 2,3-Difluoro-6-methoxybenzaldehyde

Participants

Reaction Conditions

Reaction Steps

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).

Provenance & Evidence