Potassium Carbonate → 2-Methoxy-5-(pyridin-4-yl)benzaldehyde

Participants

Reaction Conditions

Reaction Steps

To a 2-L 3-neck RB flask equipped with a mechanical stirrer, condenser with N2 inlet and temperature probe is added 3-formyl-4-methoxyphenylboronic acid P15 (49.83 g, 276.90 mmol), 4-chloropyridine hydrochloride (46.63 g, 310.84 mmol), triphenylphosphine (7.42 g, 28.28 mmol) and dimethoxyethane (280 mL). To the resulting white slurry is added 2M aqueous K2CO3 (290 mL). The resulting mixture is degassed for 20 minutes with N2 and Pd(OAc)2 (1.65 g, 7.36 mmol) is added. Under N2 atmosphere the mixture is heated to 65° C. After 47 h additional 4-chloropyridine hydrochloride (12.82 g, 85.50 mmol), triphenylphosphine (3.63 g, 13.83 mmol) and Pd(OAc)2 (632.3 mg, 2.82 mmol) is added and heating is resumed for an additional 24 h. The reaction mixture is partitioned between EtOAc (300 mL) and H2O (300 mL). The aqueous layer is extracted with EtOAc (4×400 mL) and the combined organic extracts are concentrated to a yellow-orange viscous oil. The crude reaction product is purified by filter chromatography on SiO2 eluting with EtOAc/hexanes (30 to 100%) followed by 3% MeOH/EtOAc. The yellow solid is triturated with 10% Et2O/hexanes and filtered to give 2-methoxy-5-(pyridin-4-yl)benzaldehyde P9 (53.0 g, 90%) as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 10.39 (s, 1H), 8.61 (d, J=6.10 Hz, 2H), 8.11 (d, J=8.54 Hz, 1H), 8.06 (d, J=2.20 Hz, 1H), 7.70 (d, J=5.12 Hz, 2H), 7.38 (d, J=8.78 Hz, 1H), 3.98 (s, 3H) 13C NMR (101 MHz, DMSO-d6) δ ppm 189.63, 162.77, 150.92, 146.15, 135.17, 130.03, 126.71, 125.13, 121.34, 114.37, 57.01; LRMS (ESI) Calcd for C13H11NO2 [M]: 213.079. Found [M+H]: 214.

Provenance & Evidence