2-Chloro-3-(difluoroMethyl)pyridine synthesis

Yield:865663-96-3 55%

Reaction Conditions:

with diethylamino-sulfur trifluoride in dichloromethane at 25; for 4 h;

Steps:

1.1 Step 1 : 2-chloro-3-(difluoromethyl)pyridine

To a solution of 2-chloronicotinaldehyde (5 g, 35 mmol) in dichloromethane(30 mL) was added DAST (13 mL, 100 mmol) and stirred for 4 h at 25 °C. When the starting material was consumed, the reaction was quenched with aqueous sodium bicarbonate (20 mL) at 0 °C. The mixture was extracted with dichloromethane (2 x 20 mL) and the organic layer was washed with brine (2 x 20 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and evaporated in vacuo. The resulting residue was purified by column chromatography (silica gel, 100-200 mesh, 5% ethyl acetate in hexane) affording product (3.12 g, 55%): NMR (400 MHz, chloroform-d) δ 8.50 - 8.48 (m, 1H), 8.01 - 7.97 (m, 1H), 7.39 - 7.35 (m, 1H), 7.04 - 6.76 (t, J = 54.8 Hz, 1H).

References:

WO2014/111496,2014,A1 Location in patent:Page/Page column 122