Phosphorus oxychloride → 2-Chloro-7-methoxy-1,5-naphthyridine

Participants

Reaction Conditions

Reaction Steps

A mixture of 2,7-dimethoxy-[1,5]naphthyridine (5.0 g, 26.29 mmol, 1.0 eq) and phosphorus oxychloride (4.9 mL, 52.58 mmol, 2.0 eq) in N,N-dimethylformamide (100 mL) is stirred at 0° C. for 1 hour then at 80° C. for 1 hour. The reaction mixture is cooled to 0° C., quenched with 10 mL of saturated sodium acetate aqueous solution and then stirred at 30° C. for 30 minutes. The mixture is extracted with ethyl acetate (3×60 mL). The combined organic layers are dried over sodium sulfate, filtered and concentrated to give a crude that is purified by column chromatography (silica gel, eluent: ethyl acetate:petroleum ether, 1:6, v/v) to afford 2-chloro-7-methoxy-[1,5]naphthyridine as a yellow solid (3.3 g, 64% yield).

Provenance & Evidence