反应详情

To a suspension of sodium hydride (0.062 g, 1.560 mmol) in THF (Volume: 10 mL) was added 3,3-difluoroazetidine (0.097 g, 1.040 mmol) resulting in vigorous gas evolution. After 15 minutes at room temperature, 4-chloro-5-iodopyrimidine (0.25 g, 1.040 mmol) was added as a solution in THF. After 1 h at room temperature, the reaction appeared to have proceeded only about 10%. Next, 5 mL of DMF was added and the reaction mixture was stirred at room temperature overnight. Water was carefully added to quench the reaction, followed by the addition of EtOAc. The mixture was washed once with water and then twice with brine. Next, the mixture was dried over MgSO4, filtered and concentrated to afford a brown solid. The crude material was purified by flash chromatography on silica using an ISCO machine (12 g column, 40 mL/min, 0-8% MeOH in CH2Cl2 over 15 minutes) to give Intermediate 102A (0.125 g, 0.417 mmol, 40.1% yield) as a tan solid.

1. customresulting in vigorous gas evolution
2. waitAfter 1 h at room temperature
3. customto quench
4. customthe reaction
5. washThe mixture was washed once with water
6. dry with materialNext, the mixture was dried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated
9. customto afford a brown solid
10. customThe crude material was purified by flash chromatography on silica using an ISCO machine (12 g column, 40 mL/min, 0-8% MeOH in CH2Cl2 over 15 minutes)