反应详情

A round-bottom flask was charged with perfluorophenyl 3-chloroisoquinoline-6-sulfonate (1.21 g, 2.95 mmol) and DCM (11.81 ml) to give a clear solution. Urea compound with hydrogen peroxide (1:1) (0.556 g, 5.91 mmol) was added, resulting in a suspension. The flask was cooled in an ice-water bath for 10 min, then 2,2,2-trifluoroacetic anhydride (0.834 ml, 5.91 mmol) was added over 20 s. The cooling bath was removed, the flask was sealed, and the mixture was stirred overnight for 15 h. An additional portion of TFAA (0.3 mL) was added, and the mixture was stirred for 5 h. The mixture was carefully quenched with saturated aq. sodium bicarbonate solution (50 mL), then diluted with water and extracted with DCM (3×). The cloudy organic layer was stirred over sodium sulfate for 2 min, which resulted in the formation of an orange solution. The mixture was filtered, and the filtrate was concentrated under a vacuum. The residue was dissolved in DCM (5 mL) to give an orange solution. Phosphoryl tribromide (1.693 g, 5.91 mmol) was added in one portion, and the mixture was stirred further at room temperature. After 1 h, the mixture was poured into ice, then diluted with water and DCM. When it had achieved room temperature, the layers were separated. The aq. layer was extracted with DCM (2×), and the combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The aq. layer was further diluted with water and extracted with DCM (2×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated with residue from the first organic extraction. The combined residue was purified by chromatography on silica gel (40-g Redi-Sep Gold column, 25-g loading column, 0-40% EtOAc/Heptane) to give perfluorophenyl 1-bromo-3-chloroisoquinoline-6-sulfonate (0.482 g, 0.986 mmol, 33.4% yield) as a white solid: m/z (ESI) 488.0 (M+H)+.

1. customto give a clear solution
2. customresulting in a suspension
3. temperatureThe flask was cooled in an ice-water bath for 10 min
4. customThe cooling bath was removed
5. customthe flask was sealed
6. additionAn additional portion of TFAA (0.3 mL) was added
7. stirringthe mixture was stirred for 5 h
8. customThe mixture was carefully quenched with saturated aq. sodium bicarbonate solution (50 mL)
9. additiondiluted with water
10. extractionextracted with DCM (3×)
11. stirringThe cloudy organic layer was stirred over sodium sulfate for 2 min
12. customwhich resulted in the formation of an orange solution
13. filtrationThe mixture was filtered
14. concentrationthe filtrate was concentrated under a vacuum
15. dissolutionThe residue was dissolved in DCM (5 mL)
16. customto give an orange solution
17. stirringthe mixture was stirred further at room temperature
18. waitAfter 1 h
19. additionthe mixture was poured into ice
20. customhad achieved room temperature
21. customthe layers were separated
22. extractionThe aq. layer was extracted with DCM (2×)
23. dry with materialthe combined organic extracts were dried over sodium sulfate
24. filtrationfiltered
25. concentrationconcentrated
26. additionThe aq. layer was further diluted with water
27. extractionextracted with DCM (2×)
28. dry with materialThe combined organic extracts were dried over sodium sulfate
29. filtrationfiltered
30. concentrationconcentrated with residue from the first organic extraction
31. customThe combined residue was purified by chromatography on silica gel (40-g Redi-Sep Gold column, 25-g loading column, 0-40% EtOAc/Heptane)