反应详情

To a solution of triphosgene (362 mg) in DCM (3 mL) was added pyridine (162 mg) at 0° C., and subsequently a solution of cis-2-phenylcyclohexyl amine (300 mg) in DCM (3 mL) was added dropwise thereto, followed by stirring at room temperature for 40 minutes. To a suspension of 60% oily NaH (110 mg) in THF (1.5 mL) was added 1-azabicyclo[2.2.2]oct-3-yl methanol (363 mg) at 0° C., followed by stirring at room temperature for 20 minutes, and to the mixture was added dropwise the above-described DCM solution at 0° C., followed by stirring at 80° C. for 1 hour. To the reaction mixture was added a saturated aqueous NaHCO3 solution, followed by extraction with EtOAc. The organic layer was washed with water and brine in this order, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (CHCl3:MeOH:28% aqueous ammonia=80:10:1) to obtain a colorless oily substance (100 mg). The oily substance obtained was dissolved in a mixed solvent (EtOAc:EtOH=1:1) and fumaric acid (32 mg) was added thereto. The mixture was concentrated under reduced pressure, a mixed solvent (EtOAc:IPE) was then added thereto, and the solid precipitated was collected by filtration to obtain 1-azabicyclo[2.2.2]oct-3-ylmethyl rel-[(1R,2R)-2-phenylcyclohexyl]carbamate fumarate (103 mg) as a colorless solid.

1. stirringby stirring at room temperature for 20 minutes
2. stirringby stirring at 80° C. for 1 hour
3. extractionfollowed by extraction with EtOAc
4. washThe organic layer was washed with water and brine in this order
5. dry with materialdried over MgSO4
6. concentrationconcentrated under reduced pressure
7. customThe residue was purified by silica gel column chromatography (CHCl3:MeOH:28% aqueous ammonia=80:10:1)
8. customto obtain a colorless oily substance (100 mg)
9. customThe oily substance obtained
10. additionwas added
11. concentrationThe mixture was concentrated under reduced pressure
12. additiona mixed solvent (EtOAc:IPE) was then added
13. customthe solid precipitated
14. filtrationwas collected by filtration