反应详情

温度

60 °C

A solution of 1-ethynyl-4-(methoxymethoxy)-2-methylbenzene (6-8) (1.0 equiv.), 3,5-dichloropicolinonitrile (6-9) (0.90 equiv.), CuI (0.10 equiv.), and Pd(PPh3)2Cl2 (0.10 equiv.), and triethylamine (5.0 equiv.) in DMF (0.25 M) was degassed and flushed with nitrogen. The reaction mixture was then heated to 60° C. and stirred overnight. After cooling to room temperature, water was added. The mixture was extracted with EA (2×). The combined organic layers were washed with 10% aq NH4OH (2×), brine, and concentrated. The crude material was filtered through a pad of silica (wetted with hexane). The silica was eluted with 10% EA in Hex. The fractions were combined and concentrated. The resulting solids were washed in hot ether and filtered to give a yellow solid, which was used in the next step without further purification. The filtrate was concentrated and purified by Combiflash using 0-10% EtOAc in Hexanes to give 3-chloro-5-((4-(methoxymethoxy)-2-methylphenyl)ethynyl)picolinonitrile (6-10) as a yellow solid.

1. customflushed with nitrogen
2. temperatureAfter cooling to room temperature
3. additionwater was added
4. extractionThe mixture was extracted with EA (2×)
5. washThe combined organic layers were washed with 10% aq NH4OH (2×), brine
6. concentrationconcentrated
7. filtrationThe crude material was filtered through a pad of silica (wetted with hexane)
8. washThe silica was eluted with 10% EA in Hex
9. concentrationconcentrated
10. washThe resulting solids were washed in hot ether
11. filtrationfiltered
12. customto give a yellow solid, which
13. customwas used in the next step without further purification
14. concentrationThe filtrate was concentrated
15. custompurified by Combiflash