反应详情

温度

-78 °C

Dissolve 4-fluorobromobenzene (8.75 g, 0.05 moles) in anhydrous ether (80 mL) under nitrogen atmosphere and cool to −78° C. Add dropwise 1.6 M n-BuLi (34 mL, 0.055 moles) and stir at −78° C. for 45 min. Dissolve 2,4-dichloropyrimidine (7.45 g, 0.05 moles) in Et2O (100 mL) and add dropwise to the reaction mixture. Warm the reaction mixture to −30° C. and stir at this temperature for 30 min followed by 0° C. for 30 min. Quench the reaction mixture with AcOH (3.15 mL, 0.055 moles) and water (0.5 mL, 0.027 moles) dissolved in THF (5.0 mL). Add dropwise a THF (40 mL) solution of DDQ (11.9 g, 0.053 moles) to the reaction mixture. Bring the reaction mixture to room temperature and stir at room temperature for 30 min. Cool the reaction mixture to 0° C., add 3.0 N aq. NaOH (35 mL) and stir for 30 min. Decant the organic layer from the reaction mixture and wash the brown solid with Et2O (3×100 mL). Combine the organic layers, wash several times with saturated NaCl solution and dry with MgSO4. Filter and evaporate under vacuum to afford a brown colored solid. Purify by flash column chromatography using 5% EtOAc/hexane to afford the title product as a white solid.

1. temperatureWarm the reaction mixture to −30° C.
2. stirringstir at this temperature for 30 min
3. waitfollowed by 0° C. for 30 min
4. stirringBring the reaction mixture to room temperature and stir at room temperature for 30 min
5. temperatureCool the reaction mixture to 0° C.
6. stirringstir for 30 min
7. customDecant the organic layer from the reaction mixture
8. washwash the brown solid with Et2O (3×100 mL)
9. washCombine the organic layers, wash several times with saturated NaCl solution
10. dry with materialdry with MgSO4
11. filtrationFilter
12. customevaporate under vacuum
13. customto afford a brown colored solid
14. customPurify by flash column chromatography