Cesium fluoride → Methyl 3-amino-6-bromo-2-(3-chloro-4-methoxyphenyl)isonicotinate

Participants

Reaction Conditions

Reaction Steps

A vial containing a mixture of methyl 3-amino-2,6-dibromoisonicotinate (500 mg, 1.613 mmol), 3-chloro-4-methoxyphenylboronic acid (301 mg, 1.613 mmol), cesium fluoride (588 mg, 3.87 mmol), and tetrakis(triphenylphosphine)palladium(0) (112 mg, 0.097 mmol) was flushed with nitrogen. Dimethoxyethane (8 mL) was added and the reaction was heated at 80° C. for 18 hr. It was then partitioned between EtOAc and water and the organic phase was separated, washed with brine, dried with sodium sulfate, and the solvent removed. Radial silica gel chromatography (step gradient elution with hexane containing 25 to 40% methylene chloride) afforded methyl 3-amino-6-bromo-2-(3-chloro-4-methoxyphenyl)isonicotinate (181 mg) as a yellow solid. MS (ESI) m/z 373.0 (M+H). 1H NMR (CDCl3) δ ppm 7.79 (1H, s), 7.66 (1H, d, J=2.14 Hz), 7.52 (1H, dd, J=8.55, 2.14 Hz), 7.02 (1H, d, J=8.55 Hz), 5.94 (2H, br. s.), 3.95 (3H, s), 3.92 (3H, s).

Provenance & Evidence