Phosphorus oxychloride → Ethyl 4-chloro-6-methoxy-1,5-naphthyridine-3-carboxylate

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Reaction Steps

A solution of 6-methoxy-4-oxo-1,4-dihydro-[1,5]naphthyridine-3-carboxylic acid ethyl ester (110.0 g, 407.67 mmol, 1.0 eq) in phosphorus oxychloride (650 mL) is refluxed for 4 hours. Then the reaction mixture is cooled to room temperature and the solvent is evaporated. The residue is poured into ice water and the resulting mixture is basified with 25% ammonium hydroxide to pH=8˜9 and extracted with ethyl acetate (3×500 mL). The combined organic layers are dried over sodium sulfate, filtered and evaporated to give a brown solid as crude product, which is then purified by column chromatography (silica gel, eluent: ethyl acetate:petroleum ether, 1:4, v/v) to afford 4-chloro-6-methoxy-[1,5]naphthyridine-3-carboxylic acid ethyl ester as a light yellow solid (78 g, 62% yield).

Provenance & Evidence