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

Temperature

-78 °C

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).

1. stirringstirred for 15 minutes at −78° C.
2. temperaturewarmed to room temperature
3. stirringstirred for 45 minutes
4. stirringthe reaction mixture was stirred for 5 minutes
5. washwas washed with saturated NaHCO3, water, and brine
6. dry with materialThe organic layer was dried over magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. custompurified by column chromatography (silica gel, 1-3% ethyl acetate/hexanes)

ORD record

ord-e503a0cc32654f1fa1c7b33e343d21a0

Source dataset

uspto-grants-2008_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07385066B2