反应详情

A suspension of 2-fluoro-3-hydroxybenzoic acid (12.0 g, 76.9 mmol) and potassium carbonate (23.4 g, 169 mmol) in acetone (154 mL) was stirred at ambient temperature for 1 hour. To the mixture was added dimethyl sulfate (21.8 mL, 231 mmol) and the mixture stirred at ambient temperature for 30 minutes then heated at reflux for 4 hours. The mixture was cooled to ambient temperature, filtered and concentrated under reduced pressure. The residue was dissolved in anhydrous THF (154 mL) and the solution cooled to 0° C. in an ice bath. To this solution was added LiOH—H2O (12.9 g, 307 mmol) followed by water (30 mL) and the resulting mixture stirred at ambient temperature for 3 hours. The mixture was concentrated under reduced pressure and the residue partitioned between water and ethyl acetate and the layers separated. The aqueous layer was acidified with 1N HCl solution and extracted with ethyl acetate. The combined organic extracts were washed with brine and dried (MgSO4), filtered and concentrated under reduced pressure to afford 2-fluoro-3-methoxybenzoic acid (12.31 g, 94%).

1. stirringthe mixture stirred at ambient temperature for 30 minutes
2. temperaturethen heated
3. temperatureat reflux for 4 hours
4. temperatureThe mixture was cooled to ambient temperature
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. dissolutionThe residue was dissolved in anhydrous THF (154 mL)
8. temperaturethe solution cooled to 0° C. in an ice bath
9. stirringthe resulting mixture stirred at ambient temperature for 3 hours
10. concentrationThe mixture was concentrated under reduced pressure
11. customthe residue partitioned between water and ethyl acetate
12. customthe layers separated
13. extractionextracted with ethyl acetate
14. washThe combined organic extracts were washed with brine
15. dry with materialdried (MgSO4)
16. filtrationfiltered
17. concentrationconcentrated under reduced pressure