Cesium fluoride → Methyl 3-amino-2,6-bis(4-methoxyphenyl)isonicotinate

Participants

Reaction Conditions

Reaction Steps

A mixture of methyl 3-amino-2,6-dibromoisonicotinate (500 mg, 1.61 mmol), 4-methoxyphenylboronic acid (588 mg, 3.87 mmol), Tetrakis(triphenylphosphine)-palladium(0) (93 mg, 0.081 mmol) and cesium fluoride (1176 mg, 7.74 mmol) was placed in a vial and flushed with nitrogen. Dimethoxyethane (10 mL) was added and the reaction was heated at 80° C. for 48 hr. After cooling to room temperature, the reaction was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution. The organic phase was separated, washed with saturated aqueous sodium bicarbonate solution, brine, and then dried with sodium sulfate. Removal of the solvent followed by silica gel radial chromatography (step gradient elution with hexane containing 0 to 25% ethyl acetate) afforded methyl 3-amino-2,6-bis(4-methoxyphenyl)isonicotinate (258 mg, 0.708 mmol, 43.9% yield) as a yellow oil. MS (ESI) m/z 365.2 (M+H). 1H NMR (CDCl3) δ ppm 8.01 (1H, s), 7.91 (2H, d, J=8.85 Hz), 7.66 (2H, d, J=8.55 Hz), 7.02 (2H, d, J=8.55 Hz), 6.94 (2H, d, J=8.85 Hz), 5.93 (2H, br. s.), 3.94 (3H, s), 3.86 (3H, s), 3.83 (3H, s).

Provenance & Evidence