Hydrochloric Acid → Ethyl 1-benzyl-4-hydroxy-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxylate

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Reaction Steps

Diethyl malonate (0.6 mL, 4 mmol) was added slowly to a suspension of NaH (60% in mineral oil, 164 mg, 4.1 mmol) in dimethylacetamide (20 mL) and stirred at room temperature for 0.5 h under inert atmosphere. 1-Benzyl-1H-pyrido[2,3-d][1,3]oxazine-2,4-dione (2) (1 g, 4 mmol) was added to the solution and heated at 110° C. for 4 h (TLC control). The solution was cooled and poured into ice water. The pH of the solution was adjusted to 3 by cold 10% HCl. The solids formed were filtered, washed by excess water, and dried in a vacuum oven to yield 940 mg (72%) of 1-benzyl-4-hydroxy-2-oxo-1,2-dihydro-[1,8]-naphthyridine-3-carboxylic acid ethyl ester (3) as white solids. MP: 143° C.; 1H-NMR (DMSO-d6): δ 1.29 (t, J=6.9 Hz, 3H), 4.31 (q, J=6.9 Hz, 2H), 5.55 (s, 2H), 7.23 (m, 5H), 7.36 (m, 1H), 8.45 (dd, J=1.5, 7.5 Hz, 1H), 8.70 (dd, J=1.5, 7.5 Hz, 1H); EIMS: 325 (M+1), 347 (M+23).

Provenance & Evidence