Hydrochloric Acid → 6-Fluoro-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 (10.79 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 inert atmosphere. 6-Fluoro-1-(4-methoxy-benzyl)-1H-pyrido-[2,3-d]-[1,3]-oxazine-2,4-dione (69) (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 26.01 g (98%) of 6-fluoro-4-hydroxy-1-(4-methoxy-benzyl)-2-oxo-1,2-dihydro-[1,8]-naphthyridine-3-carboxylic acid ethyl ester (74) as pale yellow solids. MP: 163° C.; 1H-NMR (DMSO-d6): δ 1.27 (t, J=7.2 Hz, 3H), 3.68 (s, 3H), 4.27 (q, J=7.0 Hz, 2H), 5.43 (s, 2H), 6.81 (m, Hz, 2H), 7.19 (m, 2H), 8.26 (dd, J=2.8, 8.0 Hz, 1H), 8.74 (d, J=2.8 Hz, 1H), 13.00 (br. S, 1H); EIMS: 373 (M+1).

Provenance & Evidence