35048-10-3

53981-25-2

56-81-5

35048-10-3

In a sealable reaction vessel, 2-amino-6-fluorophenol (4.0 g, 31.6 mmol) was dissolved in nitrobenzene (20 mL), followed by the addition of concentrated sulfuric acid (4.0 mL) in batches. Glycerol (12.0 g, 126 mmol) was added to the reaction mixture in a single addition and a change in color of the solution to dark brown was observed. After displacing the air in the reaction vessel with nitrogen, the vessel was sealed and the reaction was heated at 140 °C for 6 hours. Upon completion of the reaction, the mixture was cooled to room temperature, diluted with 30 mL of an ice-water mixture and washed three times with methyl tert-butyl ether to remove most of the nitrobenzene. Subsequently, the pH of the aqueous phase was adjusted to 6-7 by slow addition of 6 N sodium hydroxide solution. at this point, a black precipitate was generated and collected by filtration. The aqueous phase was extracted three times with ethyl acetate and the organic extract was combined with the previously collected black precipitate. The combined organic phase and precipitate were concentrated under reduced pressure and the residue was purified by silica gel column chromatography using 0-10% methanol/dichloromethane as eluent to yield 2.67 g (51.7% yield) of 7-fluoro-8-hydroxyquinoline as an off-white solid.