Potassium Phosphate, Tribasic → HCID 67469548, compound

Participants

Reaction Steps

Potassium phosphate tribasic (13.84 g, 65.2 mmol), palladium acetate (0.390 g, 1.739 mmol), methyl 2-bromo-6-methylisonicotinate (5 g, 21.73 mmol), 5-chloro-2-fluorophenylboronic acid (5.68 g, 32.6 mmol) and dicyclohexyl(2′,6′-diisopropoxybiphenyl-2-yl)phosphine (1.521 g, 3.26 mmol) were combined in toluene (70 mL) and water (14 mL) and heated at 110° C. in an oil bath for 1 hour. The reaction was then cooled and diluted with water (30 mL), filtered through Celite® and the layers were separated. The aqueous layer was extracted with ether and the combined organic layers were dried over sodium sulfate, filtered, and concentrated to give a residue. The residue was dissolved in ethyl acetate/dichloromethane and absorbed onto silica gel before chromatography on silica eluting with 10% ethyl acetate in hexanes to give an off white powder which was dissolved in dichloromethane, dried onto silica gel and further purified by chromatography on silica using a step gradient (0-10% ethyl acetate/hexanes) to give methyl 2-(5-chloro-2-fluorophenyl)-6-methylisonicotinate (1.86 g, 30.6% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.64-2.68 (3H, m) 3.91-3.95 (3H, m) 7.45 (1H, dd, J=11.12, 8.84 Hz) 7.59 (1H, ddd, J=8.84, 4.29, 2.78 Hz) 7.75-7.81 (1H, m) 8.01 (1H, dd, J=6.57, 2.78 Hz) 8.06 (1H, s). ESI-MS: m/z 280.1 (M+H).

Provenance & Evidence