Hydrochloric Acid → 3-fluoro-7-methoxyquinolin-2(1H)-one

To a solution of 3-methoxyaniline (1.718 mL, 15.29 mmol) in THF (12 mL) was added 2.5 N n-BuLi (5.965 mL, 14.91 mmol) in hexane at 0 C. The reaction mixture was stirred at 0 C for 5 minutes. (E)-methyl 3-fluoro-3-methoxyacrylate (1.00 g, 7.457 mmol) in THF (10 mL) was added. The mixture was stirred at 0° C. for one hour. 1 N HCl (20 mL) and ether (30 mL) were added. The organic layer was separated, washed with water, saturated sodium bicarbonate and brine, dried (sodium sulfate), filtered and concentrated under reduced pressure to give an oil. Sulfuric acid (70%; 8 mL) was added. The mixture was stirred at 56° C. (bath) for 2 hours. After cooling to ambient temperature, ice (20 g) and water (50 mL) were added. The mixture was stirred at ambient temperature for 10 minutes. The solid was collected by filtration and washed with water to give 3-fluoro-7-methoxyquinolin-2(1H)-one (1.40 g, 7.247 mmol, 97.19% yield) as a solid.

1. stirringThe mixture was stirred at 0° C. for one hour
2. customThe organic layer was separated
3. washwashed with water, saturated sodium bicarbonate and brine
4. dry with materialdried (sodium sulfate)
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customto give an oil
8. stirringThe mixture was stirred at 56° C. (bath) for 2 hours
9. stirringThe mixture was stirred at ambient temperature for 10 minutes
10. filtrationThe solid was collected by filtration
11. washwashed with water

ORD record

ord-90ede826846d4bd7ae05222483ce4cdc

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08889704B2