反应详情

To a solution of the 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(4-phenacyl-1-piperazinyl)-quinoline-3-carboxylic acid (0.44 g, 1 mmole) [H. Kondo et. al., J. Med. Chem., 29, 2020 (1986)] in absolute methanol (20 ml) was added a solution of hydroxylamine hydrochloride (0.14 g, 2 mmol) and sodium bicarbonate (0.17 g, 2 mmol) in water (2 ml). The mixture was heated at reflux for 36 hr and allowed to cool to room temperature. CH2Cl2 (50 ml) was added, and the layers were separated. The organic phase was washed successively with water and brine, dried over Na2SO4, filtered and concentrated in vacuo to give a solid which was purified by flash column chromatography (silica gel, with CH2Cl2/methanol (10:1) as the eluant) and crystillization from CH2Cl2/methanol (5:1) to give 1-ethyl-6-fluoro-4-oxo-7-[4-(2-hydroxyimino-2-phenylethyl)-1-piperazinyl]-1,4-dihydroquinoline-3-carboxylic acid as an off-white amorphous solid (0.31 g, 68%). Mp: 203° C. (dec). 1H NMR (DMSO-d6) δ 1.38 (t, 3H, J=7.2), 2.64 and 3.25 (two m, 8H), 3.43 and 3.73 (two s, 2 H), 4.56 (q, 2H, J=7.2), 7.15 (d, 1H, J=7.2), 7.36-7.79 (m, 5H), 7.88 (d, 1H, J=13.2), 8.92 (s, 1H), 10.99 and 11.48 (two s, 1H), 15.07 (br s, 1H). Anal. Calcd. for C24H25FN4O4•1.5 H2O: C, 60.10; H, 5.89; N, 11.68. Found: C, 60.19; H, 5.81; N, 11.64.

1. temperatureThe mixture was heated
2. temperatureat reflux for 36 hr
3. customthe layers were separated
4. washThe organic phase was washed successively with water and brine
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customto give a solid which
9. customwas purified by flash column chromatography (silica gel