Dimethylformamide → 3-Bromo-1-benzofuran-2-carbaldehyde

Temperature

-78 °C

2,3-Dibromobenzofuran (1.37 g, 5.0 mmol) is dissolved in Et2O (20 ml) in a dry flask under nitrogen and cooled to −78° C. t-Butylithium (6.47 ml, 11.0 mmol) is added drop-wise, and the chilled solution is stirred 1 h. DMF (0.45 ml, 5.75 mmol) is dissolved in Et2O (5 ml) and also added dropwise, and the mixture is stirred at −78° C. for another 4 h. The reaction is warmed to rt, whereby oxalic acid dihydrate (1.26 g, 10.0 mmol) and water (5 ml) are added. The reaction continued stirring at rt for 2 days and is then diluted with water (25 ml) and EtOAc (35 ml). The layers are allowed to separate, and the aqueous is extracted with EtOAc (1×35 ml). The organics are combined, dried over Na2SO4, filtered, and concentrated to an orange oil that solidified upon standing. The crude material is chromatographed over 100 g slurry-packed silica, eluting with 20% EtOAc/hexane. The appropriate fractions are combined and concentrated to afford 628 mg (56%) of 3-bromo-1-benzofuran-2-carbaldehyde as a yellow crystalline solid. HRMS (FAB) calcd for C9H5BrO2+H: 224.9552, found 224.9555.

1. additionis added drop-wise
2. additionalso added dropwise
3. stirringthe mixture is stirred at −78° C. for another 4 h
4. temperatureThe reaction is warmed to rt
5. stirringThe reaction continued stirring at rt for 2 days
6. customto separate
7. extractionthe aqueous is extracted with EtOAc (1×35 ml)
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated to an orange oil
11. customThe crude material is chromatographed over 100 g slurry-packed silica
12. washeluting with 20% EtOAc/hexane
13. concentrationconcentrated

ORD record

ord-2a196ef396834738b6db42086c1f5637

Source dataset

uspto-grants-2006_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07067515B2