反应详情

温度

60 °C

Potassium carbonate (3.62 g) and 2,6-dichloro-5-fluoronicotinonitrile (5.00 g) were added to a THF (50 ml) solution containing tert-butyl ((1S,2R)-2-aminocyclohexyl)carbamate (5.61 g), followed by reflux at 60° C. for 8 hours. Then, the solvent was distilled away at 70° C. 1,4-dioxane (100 ml) was added to the resulting solution, followed by stirring at 100° C. for 10 hours. The reaction solution was adjusted to room temperature. Ethyl acetate and 2M hydrochloric acid were added to the reaction solution. The organic layers were collected. The organic layers were washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was distilled away under reduced pressure and the obtained residue was purified by silica gel chromatography (n-hexane:ethyl acetate=9:1 to 2:1). Diisopropyl ether was added to the obtained oily matter and a solid precipitate was collected by filtration. A white solid of tert-butyl ((1S,2R)-2-((6-chloro-5-cyano-3-fluoropyridin-2-yl)amino)cyclohexyl)carbamate (5.77 g) was thus obtained.

1. distillationThen, the solvent was distilled away at 70° C
2. addition1,4-dioxane (100 ml) was added to the resulting solution
3. customwas adjusted to room temperature
4. additionEthyl acetate and 2M hydrochloric acid were added to the reaction solution
5. customThe organic layers were collected
6. washThe organic layers were washed with saturated saline
7. dry with materialdried over anhydrous sodium sulfate
8. distillationThe solvent was distilled away under reduced pressure
9. customthe obtained residue was purified by silica gel chromatography (n-hexane:ethyl acetate=9:1 to 2:1)
10. additionDiisopropyl ether was added to the obtained oily matter
11. filtrationa solid precipitate was collected by filtration