反应详情

To a suspension of sodium hydride (1.72 g, 43.1 mmol) in NMP (50 mL) was added a solution of 2-bromo-3-hydroxypyridine (5 g, 28.74 mmol) in NMP (50 mL). This mixture was stirred at room temperature for 30 minutes followed by heating at 50° C. for 45 minutes before cooling to room temperature. Dibromodifluoromethane (3.15 mL, 34.5 mmol) was slowly added and the mixture was stirred at room temperature for 18 hours. The reaction mixture was slowly quenched into saturated aqueous ammonium chloride (100 mL) and extracted with EtOAc (3×100 mL). The combined organic extracts were washed with water (3×100 mL), brine (2×100 mL), dried over MgSO4 and concentrated in vacuo to afford a brown gum. This residue was purified using silica gel column chromatography eluting with 70/30 Heptane/EtOAc to give the title compound as a colourless oil (1.2 g, 14%).

1. temperatureby heating at 50° C. for 45 minutes
2. temperaturebefore cooling to room temperature
3. stirringthe mixture was stirred at room temperature for 18 hours
4. customThe reaction mixture was slowly quenched into saturated aqueous ammonium chloride (100 mL)
5. extractionextracted with EtOAc (3×100 mL)
6. washThe combined organic extracts were washed with water (3×100 mL), brine (2×100 mL)
7. dry with materialdried over MgSO4
8. concentrationconcentrated in vacuo
9. customto afford a brown gum
10. customThis residue was purified
11. washeluting with 70/30 Heptane/EtOAc