Sodium Carbonate → Methyl 3-amino-2-(4-(benzyloxy)phenyl)-6-bromoisonicotinate

Participants

Reaction Steps

A mixture of 4-(benzyloxy)phenylboronic acid (3.53 g, 15.5 mmol), methyl 3-amino-2,6-dibromoisonicotinate (4.0 g, 12.9 mmol), tetrakis(triphenylphosphine)-palladium(0) (0.90 g, 0.77 mmol), sodium carbonate (3.28 g, 31.0 mmol) was flushed with nitrogen and toluene (32 mL), and MeOH (11 mL) were added. The reaction was heated at reflux under nitrogen for 24 hr. It was partitioned between EtOAc and water. The organic phase was washed with brine, dried with sodium sulfate and the solvent removed. Radial chromatography (step gradient elution with hexane containing 20 to 80% DCM) afforded methyl 3-amino-2-(4-(benzyloxy)phenyl)-6-bromoisonicotinate (3.28 g, 7.94 mmol, 62% yield) as a yellow solid. MS (ESI) m/z 415.0 (M+H). 1H NMR (500 MHz, chloroform-d) δ ppm 7.77 (1H, s), 7.52-7.58 (2H, m), 7.41-7.46 (2H, m), 7.36-7.41 (2H, m), 7.30-7.36 (1H, m), 7.04-7.09 (2H, m), 5.95 (2H, br. s.), 3.92 (3H, s).

Provenance & Evidence