反应详情

温度

115 °C

A flask was charged with 5-bromo-4-fluoro-2-iodobenzoic acid (4.00 g, 11.60 mmol), 6-chloropyridin-3-ol (1.803 g, 13.92 mmol), and cesium carbonate (7.56 g, 23.19 mmol). The flask was evacuated and flushed with nitrogen twice before copper (I) trifluoromethanesulfonate toluene complex (0.156 g, 0.302 mmol) was added. Toluene (58.0 mL) (degassed 10 minutes by bubbling nitrogen through the solution prior to use) and ethyl acetate (0.084 mL, 0.858 mmol) were added and the mixture was heated at 115° C. After 2 hours, the reaction was allowed to cool to RT and the mixture was diluted with water (50 mL) and stirred vigorously for 15 minutes. After diluting with ether (200 mL), the layers were separated and the organic layer was extracted with 10% sodium carbonate. The pH of the combined aqueous layers was adjusted to pH ˜2 and extracted with ethyl acetate. The combined organic layers were washed with saturated sodium chloride, dried over sodium sulfate, filtered, and concentrated to afford 5-bromo-2-(6-chloropyridin-3-yloxy)-4-fluorobenzoic acid as a solid. MS m/z=347.9 [M+H].

1. customThe flask was evacuated
2. customflushed with nitrogen twice before copper (I) trifluoromethanesulfonate toluene complex (0.156 g, 0.302 mmol)
3. additionwas added
4. customToluene (58.0 mL) (degassed 10 minutes
5. customby bubbling nitrogen through the solution
6. additionwere added
7. temperatureto cool to RT
8. customthe layers were separated
9. extractionthe organic layer was extracted with 10% sodium carbonate
10. extractionextracted with ethyl acetate
11. washThe combined organic layers were washed with saturated sodium chloride
12. dry with materialdried over sodium sulfate
13. filtrationfiltered
14. concentrationconcentrated