Carbon tetrabromide → 4-Bromo-1-(bromomethyl)-2-(trifluoromethyl)benzene

Treat a mixture of 4-bromo-2-(trifluoromethyl)benzaldehyde (6.52 g, 25.8 mmol) and methanol (250 mL) in a 500 mL flask with sodium borohydride (778 mg, 20.6 mmol). Stir the reaction at room temperature for 1 hour then dilute with ethyl acetate (300 mL). Wash with water (2×200 mL) and saturated sodium chloride solution (1×200 mL), then dry over anhydrous magnesium sulfate. After filtering, concentrate the solution under vacuum to dryness. Add dimethylformamide (250 mL) to the residue and cool in an ice bath before treating with carbon tetrabromide (12.78 g, 38.5 mmol) and triphenylphosphine (10.11 g, 38.5 mmol) for 3 hours. Add ethyl acetate (300 mL) and wash with water (2×200 mL) then saturated sodium chloride solution (1×200 mL). Dry over anhydrous magnesium sulfate and concentrate under vacuum. Purify the crude product via silica gel chromatography eluting with hexanes to afford 6.02 g (74%) of the product as a clear oil: 1H NMR (300 MHz, CDCl3) δ 7.78 (d, 1H, J=1.9 Hz), 7.68 (dd, 1H, J=1.9 Hz, J=8.3 Hz), 7.47 (d, 1H, J=8.3 Hz), 4.57 (s, 2H).

1. additionTreat
2. customthe reaction at room temperature for 1 hour
3. washWash with water (2×200 mL) and saturated sodium chloride solution (1×200 mL)
4. dry with materialdry over anhydrous magnesium sulfate
5. filtrationAfter filtering
6. concentrationconcentrate the solution under vacuum to dryness
7. temperatureAdd dimethylformamide (250 mL) to the residue and cool in an ice bath
8. washAdd ethyl acetate (300 mL) and wash with water (2×200 mL)
9. dry with materialDry over anhydrous magnesium sulfate
10. concentrationconcentrate under vacuum
11. customPurify the crude product via silica gel chromatography
12. washeluting with hexanes

ORD record

ord-17eaf584a1eb41f199c4c23c0bf9328d

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08088776B2