Citric Acid → 4-Bromo-5-chlorothiophene-2-carbaldehyde

Participants

Reaction Conditions

Reaction Steps

To a −78° C. solution of 3-bromo-2-chloro-thiophene (10.03 g, 50.79 mmol) in THF (anhydrous, 100 mL) was added lithium diisopropyl amide solution (Aldrich, 2.0M in heptane/THF/ethylbenzene, 38.1 mL, 76.20 mmol) dropwise over 45 minutes under argon. The reaction mixture was stirred for one hour at −78° C., treated with DMF (Aldrich, anhydrous, 19.7 mL, 254.40 mmol), stirred for 15 minutes at −78° C., warmed to room temperature, and stirred for 45 minutes. Aqueous citric acid was added and the reaction mixture was stirred for 5 minutes. The mixture was diluted with ethyl acetate and was washed with saturated NaHCO3, water, and brine. The organic layer was dried over magnesium sulfate, filtered, concentrated in vacuo, and purified by column chromatography (silica gel, 1-3% ethyl acetate/hexanes) to afford the title compound as a yellow solid (10.63 g, 92.8% yield).

Provenance & Evidence