反应详情

4-(4-Benzyloxycarbonylamino-2-fluorophenoxy)pyridine-2-carboxylic acid methyl ester (10.7 g) was dissolved in methanol (450 ml) and N,N-dimethylformamide (150 ml), and water (75 ml) and lithium hydroxide (1.36 g) were added thereto, followed by stirring at room temperature for 1 hr. 1N hydrochloric acid (100 ml) was added thereto, then the reaction mixture was concentrated under reduced pressure and liquid-liquid separation was carried out after addition of ethyl acetate (500 ml), and the precipitated solid was collected by filtration. The resultant solid was washed with water and hexane, and dried under aeration. The organic layer of the filtrate obtained above was washed with water (100 ml×2) and brine (200 ml) and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the resultant solid was washed with water and hexane and dried under aeration. This solid was combined with the solid obtained above, and dried at 60° C. overnight to provide the titled compound as white powder (9.53 g, 92.3%).

1. concentrationthe reaction mixture was concentrated under reduced pressure and liquid-liquid separation
2. additionafter addition of ethyl acetate (500 ml)
3. filtrationthe precipitated solid was collected by filtration
4. washThe resultant solid was washed with water and hexane
5. customdried under aeration
6. customThe organic layer of the filtrate obtained
7. washabove was washed with water (100 ml×2) and brine (200 ml)
8. dry with materialdried over anhydrous sodium sulfate
9. customThe solvent was removed under reduced pressure
10. washthe resultant solid was washed with water and hexane
11. customdried under aeration
12. customobtained above, and
13. customdried at 60° C. overnight