Ammonium Hydroxide → 3-Fluoro-7-methoxy-2-methylquinoline

Temperature

-78 °C

To a suspension of Cu(I)Br (1.49 g, 10.4 mmol) in THF (30 mL) was added 3M MeMgBr (6.93 ml, 20.8 mmol) in ether at −78° C. After stirring at −78° C. for 5 minutes, 2-chloro-3-fluoro-7-methoxyquinoline (0.55 g, 2.60 mmol) in THF (10 mL) was added. The reaction mixture was stirred at −78° C. for 1 hour, then allowed to warm to ambient temperature and stirred for 20 hours. Ammonium hydroxide (10 mL) was added slowly. The mixture was stirred at ambient temperature for 10 minutes, then passed through a pad of Celite® and washed with ether (50 mL). The filtrated was washed with brine (20 mL), dried (sodium sulfate), filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography 3:1 hexane/ethyl acetate to give 3-fluoro-7-methoxy-2-methylquinoline (0.255 g, 1.33 mmol, 51.3% yield) as a solid.

1. stirringThe reaction mixture was stirred at −78° C. for 1 hour
2. temperatureto warm to ambient temperature
3. stirringstirred for 20 hours
4. stirringThe mixture was stirred at ambient temperature for 10 minutes
5. washwashed with ether (50 mL)
6. washThe filtrated was washed with brine (20 mL)
7. dry with materialdried (sodium sulfate)
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe crude residue was purified by flash chromatography 3:1 hexane/ethyl acetate

ORD record

ord-8a260a8e56c74e0d8bf78091058a2f08

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08889704B2