反应详情

温度

106 °C

A solution of tert-butyl 2-fluoro-3-methoxyphenylcarbamate (2.27 g, 9.41 mmol) in methanol (5 mL) was treated with 4N HCl in 1,4-dioxane (30 mL) for 2 hours. The solvent was removed under reduced pressure and the residue stirred in aqueous 6N HCl (20 mL) at 106° C. A solution of crotonaldehyde (1.56 mL, 18.8 mmol) in n-BuOH (2 mL) was added dropwise from an addition funnel over 20 minutes and the resulting mixture was heated at reflux for an additional 2 hours. The reaction was cooled to ambient temperature and the mixture carefully pH adjusted to 9 with ammonium hydroxide. The mixture was extracted with dichloromethane and the combined dichloromethane extracts were dried (MgSO4), filtered and concentrated under reduced pressure. The residue was purified by column chromatography (Biotage 40M; 10% ethyl acetate/hexanes) to afford 8-fluoro-7-methoxy-2-methylquinoline (1.20 g, 6.28 mmol, 67%).

1. customThe solvent was removed under reduced pressure
2. temperaturethe resulting mixture was heated
3. temperatureat reflux for an additional 2 hours
4. temperatureThe reaction was cooled to ambient temperature
5. extractionThe mixture was extracted with dichloromethane
6. dry with materialthe combined dichloromethane extracts were dried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe residue was purified by column chromatography (Biotage 40M; 10% ethyl acetate/hexanes)