反应详情

A mixture of 2-fluoro-5-nitrobenzoic acid (600 mg) and thionyl chloride (2 mL) was heated under reflux for 15 hours. The reaction liquid was concentrated under reduced pressure, followed by an azeotropic process with toluene to give a yellow crystal. To a mixture of the yellow crystal and THF (11 mL), triethylamine (0.47 mL) and isopropylamine (0.29 mL) were added under ice cooling and stirred at room temperature for 5 hours. The reaction liquid was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and then dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to give a yellow crystal. To a mixture of the yellow crystal (723 mg) and methanol (8 mL) and water (3 mL), ammonium chloride (2.05 g) and zinc powder (2.09 g) were added, and the mixture was heated under reflux for 3 hours. After filtration of the reaction suspension through celite, the filtrate was concentrated under reduced pressure. The residue was poured into saturated aqueous sodium hydrogen carbonate and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and then dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent; chloroform:methanol) to give 5-amino-2-fluoro-N-isopropylbenzamide (527 mg) as a light brown crystal.

1. temperaturewas heated
2. temperatureunder reflux for 15 hours
3. customThe reaction liquid
4. concentrationwas concentrated under reduced pressure
5. customto give a yellow crystal
6. additionwere added under ice cooling
7. customThe reaction liquid
8. extractionextracted with ethyl acetate
9. washThe organic layer was washed with saturated aqueous sodium chloride
10. dry with materialdried over anhydrous sodium sulfate
11. distillationthe solvent was distilled off under reduced pressure
12. customto give a yellow crystal
13. additionwere added
14. temperaturethe mixture was heated
15. temperatureunder reflux for 3 hours
16. filtrationAfter filtration of the reaction suspension through celite
17. concentrationthe filtrate was concentrated under reduced pressure
18. additionThe residue was poured into saturated aqueous sodium hydrogen carbonate
19. extractionextracted with ethyl acetate
20. washThe organic layer was washed with saturated aqueous sodium chloride
21. dry with materialdried over anhydrous sodium sulfate
22. distillationthe solvent was distilled off under reduced pressure
23. customThe residue was purified by silica gel column chromatography (eluent; chloroform:methanol)