Dimethylformamide → 2-(4-Bromo-2,6-difluorophenyl)acetyl chloride

Temperature

60 °C

To a solution of 2-(4-bromo-2,6-difluorophenyl)acetic acid (0.3 g, 1.195 mmol) in sulfurous dichloride (5 mL, 1.195 mmol) was added DMF (9.25 μL, 0.120 mmol). The resulting mixture was stirred at 60° C. After 2 h, LCMS analysis showed the starting material had disappeared and the solvent was removed in vacuo to give 2-(4-bromo-2,6-difluorophenyl)acetyl chloride (0.35 g, 0.832 mmol, 69.6% yield). To a solution of 4-(2-(benzyloxy)ethoxy)-3-(trifluoromethyl)aniline (0.347 g, 1.113 mmol) and Et3N (0.225 g, 2.227 mmol) in DCM (30 mL) was added 2-(4-bromo-2,6-difluorophenyl)acetyl chloride (0.3 g, 1.113 mmol). The resulting mixture was stirred at 25° C. After LCMS analysis showed the starting material had disappeared, the mixture was washed with H2O (20 mL) and brine (20 mL). The organic layer was dried over Na2SO4, filtered and concentrated to give the crude product, which was purified by preparative TLC (PE/EA=3/1) to give N-(4-(2-(benzyloxy)ethoxy)-3-(trifluoromethyl)phenyl)-2-(4-bromo-2,6-difluoro phenyl)acetamide (110 mg, 0.196 mmol, 17.6% yield): 1H NMR (400 MHz, CD3OD) δ 7.81 (d, J=2.8 Hz, 1H), 7.68 (d, J=2.4 Hz, 1H), 7.32-7.25 (m, 7H), 7.15 (d, J=8.8 Hz, 1H), 4.61 (s, 2H), 4.23 (t, J=4.6 Hz, 2H), 3.84 (t, J=4.6 Hz, 2H), 3.77 (s, 2H); ES-LCMS m/z 546.0 (M+H).

1. customthe solvent was removed in vacuo

ORD record

ord-7c3254952d544971a10aca4c74b651a6

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08937071B2