Sodium Methoxide → 7-Chloro-1,5-naphthyridin-2(1H)-one

Participants

Reaction Steps

A suspension of (E)-methyl 3-(3-amino-5-chloropyridin-2-yl)acrylate (1.2 g, 5.64 mmol) and sodium methoxide (0.786 ml, 14.11 mmol) in 20 mL of ethanol was refluxed for 3 h until the starting material disappeared. The reaction mixture was evaporated to dryness to give crude product 7-chloro-1,5-naphthyridin-2(1H)-one. To the crude residue was added phosphorus oxychloride (5.17 ml, 56.4 mmol) and the resulting mixture was stirred at 70° C. for 4 h. The excess POCl3 was removed under reduced pressure and the residue was directly submitted to flash column (DCM) to give 2,7-dichloro-1,5-naphthyridine (540 mg, 2.71 mmol, 48.1% yield) as an off-white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm=8.90 (d, J=2.2 Hz, 1H), 8.35 (d, J=8.8 Hz, 1H), 8.31 (d, J=1.8 Hz, 1H), 7.63 (d, J=8.8 Hz, 1H). m/z=199 (M+1).

Provenance & Evidence