1-Bromo-4-(1,1-difluoropropyl)benzene synthesis

Yield:162783-79-1 54.5%

Reaction Conditions:

with diethylamino-sulfur trifluoride in dichloromethane at -70 - 50; for 72 h;

Steps:

V.20.1 Synthesis of 1-bromo-4-(1, 1-difluoropropyl) benzene [5.20a].

1-(4-Bromophenyl) propan-1-one (0.5 g, 2.3 mmol, 1.0 equiv) was dissolved in dichloromethane (10 mL) and cooled to -70 °C. DAST (1.89 g, 11.7 mmol, 5.0 equiv) was added drop wise and the reaction mixture was stirred at rt for 24 hours. The reaction mixture was stirred at 50°C for 48 hours. The reaction mixture was quenched with water, neutralized by saturated aqueous sodium bicarbonate solution and extracted with EtOAc. The organic layer was washed with brine, dried over sodium sulfate and concentrated to afford a crude residue. The crude residue was purified by silica gel chromatography (100 % hexane) to afford the desired product 5.20a (0.3 g, 54.5 % yield). 1H NMR (400 MHz, CDCI3) 6 7.59 (t, J = 9.5 Hz, 2H), 7.36 (d, J= 8.6 Hz, 2H), 2.12 (ddd, J= 16.5, 12.5, 4.5 Hz, 2H), 1.00 (t, J 7.5 Hz, 3H).

References:

WO2015/66413,2015,A1 Location in patent:Page/Page column 176