2-Bromo-4-(difluoromethyl)pyridine synthesis

Yield:1204295-87-3 90%

Reaction Conditions:

with diethylamino-sulfur trifluoride in dichloromethane at -78 - 20; for 2 h;

Steps:

a (a) 2-bromo-4-(difluoromethyl)pyridine

To a solution of 2-bromoisonicotinaldehyde (2g, 10.752 mmol) in dichloromethane was added DAST( 6.613g, 32.257 mmol) at -78 °C. The mixture was warmed to room temperature slowly in 2 hours. The reaction mixture was quenched with saturated sodium bicarbonate and extracted with dichloromethane. The combined organic layer was washed with brine, dried over anhydrous sodium sulfate and evaporated to give 2-bromo-4-(difluoromethyl)pyridine (2 g, yield 90%).¹HNMR (400MHz, CDCls): 5=8.52-8.51 (d, / = 8.0 Hz, 1 H), 7.63 (s, 1 H), 7.40-7.38 (d, / = 8.0 Hz, 1 H), MS (ESI): M/Z (M+l)=207.95.

References:

WO2014/114185,2014,A1 Location in patent:Page/Page column 159