Methanol → 5-(4-Methoxyphenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile

Participants

Reaction Steps

To a stirred solution of sodium hydride (60% dispersion in mineral oil, 4.5 g, 112 mmol) in N,N-dimethylformamide (100 mL) was added dropwise at 0° C. a solution of crude 4-dimethylamino-3-(4-methoxyphenyl)-but-3-en-2-one (3) from the previous step, 2-cyano-acetamide (4, 4.75 g, 56.5 mmol) and methanol (4.54 mL, 112 mmol) in N,N-dimethylformamide (50 mL). The reaction mixture was stirred at ambient temperature for 15 min and then at 95° C. for 18 h. After cooling to ambient temperature most of the solvent was removed under reduced pressure. The residue was hydrolysed with saturated aqueous ammonium chloride solution (100 mL). The precipitated solid was collected by filtration with suction, rinsed with water and diethyl ether and dried under vacuum to give 5-(4-methoxy-phenyl)-6-methyl-2-oxo-1,2-dihydro-pyridine-3-carbonitrile (5) as a brownish solid (10.0 g, 82% yield over two steps, 99% pure by LC-MS and 1H NMR), 1H NMR (400 MHz; CDCl3): δ 7.70 (s, 1H); 7.19 (m, 2H); 6.72 (m, 2H); 3.73 (s, 3H); 1.71 (s, 3H).

Provenance & Evidence