Glycerol → 7-Fluoroquinolin-8-ol

Temperature

140 °C

To a solution of 2-amino-6-fluorophenol (4.0 g, 31.6 mmol) and nitrobenzene (20 mL) in a sealable reaction vessel was added in portions sulfuric acid (4.0 mL). Glycerol (12.0 g, 126 mmol) was added in one portion, and the solution turned to dark brown. The vessel was flushed with nitrogen, sealed and heated to 140° C. for 6 h. The reaction mixture was cooled to rt, diluted with 30 mL ice/water mixture, and washed 3 times with methyl t-butyl ether (removes most of the nitrobenzene). The aqueous phase was neutralized to pH=6-7 by slow addition of 6N NaOH. The resulting black precipitate was collected and the water solution was extracted with ethyl acetate 3 times. The organic extracts were combined with the black precipitate, concentrated in vacuo, and purified on silica gel column with 0-10% MeOH/DCM to give 2.67 g (51.7%) of 7-fluoro-8-quinolinol as an off-white solid.

1. customThe vessel was flushed with nitrogen
2. customsealed
3. temperatureThe reaction mixture was cooled to rt
4. additiondiluted with 30 mL ice/water mixture
5. washwashed 3 times with methyl t-butyl ether (
6. customremoves most of the nitrobenzene)
7. additionThe aqueous phase was neutralized to pH=6-7 by slow addition of 6N NaOH
8. customThe resulting black precipitate was collected
9. extractionthe water solution was extracted with ethyl acetate 3 times
10. concentrationconcentrated in vacuo
11. custompurified on silica gel column with 0-10% MeOH/DCM

ORD record

ord-b0c9b934a8274be9883aa0226e1caf1c

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09034303B2