Cesium fluoride → Methyl 4-amino-6-(4-chloro-3-fluorophenyl)-5-fluoropicolinate

Participants

Reaction Conditions

Reaction Steps

Methyl 4-amino-6-chloro-5-fluoropicolinate (3.0 g, 14.66 mmol), (4-chloro-3-fluorophenyl)boronic acid (3.07 g, 17.60 mmol), bis(triphenylphosphine)palladium(II) dichloride (1.029 g, 1.466 mmol), and cesium fluoride (4.45 g, 29.3 mmol) were comined in a flask that was sealed and purged with nitrogen. Dioxane (50 ml) and Water (10.00 ml) were added and the reaction mixture was heated at 85° C. for 18 hrs. The reaction mixture was diluted with ethyl acetate and water. The organic phase was washed with saturated sodium chlride, dried over magnesium sulfate, filtered, and concentrated onto silica. The product was purified by flash chromatography (SiO2, 0-40% EtOAc:Hex gradient) to provide the title compound (3.11 g, 10.41 mmol, 71.0% yield) as a white solid: 1H NMR (400 MHz, DMSO-d6) d 3.85 (s, 3H), 6.72 (s, 2H), 7.49 (d, J=6.3 Hz, 1H), 7.68-7.80 (m, 2H), 7.84 (dd, J=10.8, 1.3 Hz, 1H); 19F NMR (376 MHz, DMSO-d6) d −144.47, −116.07; ESIMS m/z 299 ([M+H]+).

Provenance & Evidence