1-Bromo-2-chloro-4-(difluoromethyl)benzene synthesis

Yield:1261614-16-7 68.2%

Reaction Conditions:

with (bis-(2-methoxyethyl)amino)sulfur trufluoride in tetrahydrofuran;ethanol;dichloromethane at 22; for 20 h;

Steps:

24

Intermediate 24: l-Bromo-2-chloro-4-(difluoromethyl)benzene Ethanol (0.053 mL, 0.91 mmol) was added to 4-bromo-3-chlorobenzaldehyde (1 g, 4.56 mmol) and Deoxo-Fluor(R) (50% in THF) (3.36 mL, 7.75 mmol) in DCM (20 mL) at 22°C. The resulting solution was stirred at 22 °C for 20 hours. The reaction mixture was quenched with saturated NaHC0₃ (100 mL), extracted with DCM (2 x 150 mL), the organic layer was dried over Na₂S0₄, filtered and evaporated to afford a yellow liquid. The crude product was purified by flash alumina chromatography, elution gradient 1 to 5% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford the title compound (0.750 g, 68.2 %) as a colourless liquid, containing 4.5% starting aldehyde by NMR. The product was used in subsequent reactions without further purification1H NMR (400 MHz, CDC1₃) 6.59 (1H, td), 7.23 - 7.29 (1H, m), 7.60 (1H, s), 7.72 (1H, d).

References:

WO2011/121350,2011,A1 Location in patent:Page/Page column 104