反应详情

温度

50 °C

To a mixture of 2-(3-piperidin-4-ylidenemethyl-phenoxy)-5-trifluoromethyl-pyridine (80.0 g, 0.216 mol) and phenyl pyridin-3-ylcarbamate (48.6 g, 0.227 mol) in acetonitrile (650 mL) was added dropwise diisopropylethyl amine (55.8 g, 0.432 mol). A solution formed after ˜45 min of stirring. The slightly turbid solution was stirred at ambient temperature for 18 h. TLC showed a prominent product spot with traces of both starting materials and two other fast moving spots. The solution was concentrated in vacuo to a viscous oil. This was partitioned between dichloromethane (600 mL) and water (500 mL). The aqueous layer was extracted with 200 mL of dichloromethane. The combined organic layers were washed with successive portions of 500 mL of 5% sodium hydroxide, and 200 mL of water, then dried over magnesium sulfate and concentrated in vacuo to 139.5 g of a viscous oil. This was dissolved in 350 mL of warm (50° C.) methyl t-butyl ether. Soon after a solution formed, solid began separating. The crystallizing mixture was kept at −10° C. for 4 h and filtered. The solid was rinsed with 60 mL of methyl t-butyl ether and pressed dry under suction. Further drying in vacuo at 28° C. for 16 h and then at 35° C. for 6 h provided 93.2 g (95%) of product.

1. customA solution formed after ˜45 min
2. stirringThe slightly turbid solution was stirred at ambient temperature for 18 h
3. concentrationThe solution was concentrated in vacuo to a viscous oil
4. customThis was partitioned between dichloromethane (600 mL) and water (500 mL)
5. extractionThe aqueous layer was extracted with 200 mL of dichloromethane
6. washThe combined organic layers were washed with successive portions of 500 mL of 5% sodium hydroxide, and 200 mL of water
7. dry with materialdried over magnesium sulfate
8. concentrationconcentrated in vacuo to 139.5 g of a viscous oil
9. dissolutionThis was dissolved in 350 mL
10. customSoon after a solution formed
11. customsolid began separating
12. filtrationfiltered
13. washThe solid was rinsed with 60 mL of methyl t-butyl ether
14. custompressed dry under suction
15. customFurther drying in vacuo at 28° C. for 16 h