反应详情

Potassium carbonate (3.02 g, 21.85 mmol) was added portionwise to a suspension of tert-butyl 5-chloro-2,4-difluorobenzoate (Preparation 59, 2.26 g, 9.09 mmol), 5-chloro-6-(2,2,3,3-tetrafluoropropoxy)pyridin-3-ol (Preparation 73, 2.25 g, 8.67 mmol) in DMSO (13.5 mL). The mixture was stirred at room temperature under nitrogen for 3 hours. tert-butyl methyl ether (50.0 mL) was added and the mixture was washed with water (3×50.0 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting oil was suspended with heptane (20.0 mL) and concentrated in vacuo. The resulting solid was suspended in heptane (20.0 mL) and heated to 90° C. until full dissolution. The mixture was cooled with stirring and the residual solid collected by filtration. The filtrate was concentrated in vacuo and the resulting solid was suspended in heptane (10.0 mL) and heated to 90° C. until dissolution. The mixture was again cooled with stirring and the residual solid collected by filtration. The two crops were combined to yield the title compound as a white solid (2.58 g, 5.29 mmol, 61%):

1. washthe mixture was washed with water (3×50.0 mL)
2. dry with materialThe organic layer was dried over sodium sulfate
3. filtrationfiltered
4. concentrationconcentrated in vacuo
5. concentrationconcentrated in vacuo
6. temperatureheated to 90° C. until full dissolution
7. temperatureThe mixture was cooled
8. stirringwith stirring
9. filtrationthe residual solid collected by filtration
10. concentrationThe filtrate was concentrated in vacuo
11. temperatureheated to 90° C. until dissolution
12. temperatureThe mixture was again cooled
13. stirringwith stirring
14. filtrationthe residual solid collected by filtration