Glycerol → 6-Bromo-7-fluoroquinoline

Participants

Reaction Conditions

Reaction Steps

To a suspension of 4-bromo-3-fluoro-phenylamine (100.0 g, 526 mmol) in concentrated sulfuric acid (290 mL) was added glycerol (220.0 g, 2.39 mol, 4.5 eq.) followed by ferrous sulfate (30.0 g, 0.2 eq.). The reaction mixture was heated at 130° C. for 14 h, cooled to it and poured onto ice-water. The solution was adjusted with saturated aqueous ammonium hydroxide to pH 8 and extracted with DCM (2 L×3). The combined organic layers were washed with brine (1 L×3), dried over Na2SO4 and concentrated under reduced pressure to afford a crude product, which was purified by column chromatography (petroleum:EtOAc=10:1) to give the title compound as white solid (45 g, 39%). 1H-NMR (400 MHz, DMSO-d6) ppm 8.86 (s, 1H), 8.56 (m, 1H), 8.45 (m, 1H), 7.90 (d, 1H), 7.71 (m, 1H).

Provenance & Evidence