Diethoxymethane → 2-Methoxy-5-(pyridin-4-yl)benzaldehyde

Participants

Reaction Conditions

Reaction Steps

To a 1 L 3-neck RB flask equipped with a N2 inlet, condenser and temperature probe is added 3-formyl-4-methoxyphenylboronic acid P15 (25.62 g, 142.38 mmol), 4-chloropyridine hydrochloride (23.65 g, 157.66 mmol), triphenylphosphine (3.77 g, 14.37 mmol), diethoxymethane (140 mL), and a solution of K2CO3 (2.7M, 150 mL). The yellow slurry is degassed with N2 for 10 minutes and Pd(OAc)2 (840.9 mg, 3.74 mmol) is added. The mixture is heated to 80° C. for 19 h. The layers are separated and the aqueous layer is extracted with EtOAc. The combined organic extracts are concentrated in vacuo and purified by filter chromatography on SiO2 eluting with EtOAc/hexanes (30 to 100%) followed by 3% MeOH/EtOAc, to give 2-methoxy-5-(pyridin-4-yl)benzaldehyde P9 (29.97 g, 99%) as a yellow solid. (L30464-208, 266146). To remove excess palladium 2-methoxy-5-(pyridin-4-yl)benzaldehyde P9 (28.26 g, 132.53 mmol) in EtOAc (500 mL) is treated with N-acetylcysteine (2.22 g, 13.58 mmol) in H2O (100 mL). The mixture is stirred for 4 h diluted with H2O and the layers are separated. The aqueous layer is extracted with EtOAc (5×200 mL) and the combined organic extracts are concentrated in vacuo and filtered through a Magnesol pad to give 2-methoxy-5-(pyridin-4-yl)benzaldehyde P9 (25.33 g, 90%) as a yellow solid.

Provenance & Evidence