Hydrochloric Acid → 6-Chloro-4-hydroxy-1-(4-methoxy-benzyl)-2-oxo-1,2-dihydro-[1,8]-naphthyridine-3-carboxylic Acid Ethyl Ester

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Reaction Steps

Diethyl malonate (6.02 mL, 71.38 mmol) was added slowly to a suspension of NaH (60% in mineral oil, 3.13 g, 78.24 mmol) in dimethylacetamide (200 mL) and stirred at room temperature for 0.5 h under argon atmosphere. 6-Chloro-1-(4-methoxy-benzyl)-1H-pyrido-[2,3-d]-[1,3]-oxazine-2,4-dione (73) (21.5 g, 71.31 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 14.0 g (99%) of 6-chloro-4-hydroxy-1-(4-methoxy-benzyl)-2-oxo-1,2-dihydro-[1,8]-naphthyridine-3-carboxylic acid ethyl ester (75) as white solids. MP: 198° C.; 1H-NMR (DMSO-d6): δ 1.28 (t, J=7.2 Hz, 3H), 3.68 (s, 3H), 4.30 (q, J=7.2 Hz, 2H), 5.43 (s, 2H), 6.81 (m, Hz, 2H), 7.20 (m, 2H), 8.43 (d, J=2.8 Hz, 1H), 8.74 (d, J=2.8 Hz, 1H); EIMS: 389 (M+1).

Provenance & Evidence