反应详情

温度

60 °C

A solution of 1-ethynyl-4-(methoxymethoxy)-2-methylbenzene (8) (1.0 equiv.), 3,5-dichloropicolinonitrile (9) (0.90 equiv.), CuI (0.10 equiv.), and Pd(PPh3)2Cl2 (0.10 equiv.), and triethylamine (5.0 equiv.) in DMF (0.25M) 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 (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