Glycerol → 6-Bromo-7-fluoroquinoline

Temperature

130 °C

To a suspension of 4-bromo-3-fluoro-phenylamine (100 g, 526 mmol) in concentrated sulfuric acid (290 mL) was added glycerol (220 g, 2.39 mol, 4.5 eq.) followed by ferrous sulfate (30 g, 0.2 eq.). The reaction mixture was heated at 130° C. for 14 h, cooled to rt and poured into ice-water. The solution was neutralized 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 sodium sulfate and concentrated under reduced pressure to afford the crude product as a brown solid, which was purified by column chromatography (Petroleum:Ethyl acetate=10:1) to give 6-bromo-7-fluoro quinoline as a white solid (45 g, 39%). 1H-NMR (400 MHz, DMSO-d6) δ ppm 8.86 (s, 1H), 8.56 (m, 1H), 8.45 (m, 1H), 7.90 (d, 1H), 7.71 (m, 1H).

1. temperaturecooled to rt
2. extractionextracted with DCM (2 L×3)
3. washThe combined organic layers were washed with brine (1 L×3)
4. dry with materialdried over sodium sulfate
5. concentrationconcentrated under reduced pressure
6. customto afford the crude product as a brown solid, which
7. customwas purified by column chromatography (Petroleum:Ethyl acetate=10:1)

ORD record

ord-a97c4c06666540f6b30f04b9cf373f0d

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08497368B2