反应详情

Ethyldiisopropylamine (194 μL) and benzylchloroformate (137 μL) were added dropwise to (2S,4S)-1-[[N-[4-(2-tetrahydropyranyl)oxycarbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (379 mg) in dioxane (5 mL) while the solution was cooled in water. The mixture was stirred at room temperature for 1 hour, followed by addition of 1N hydrochloric acid (0.1 mL) and stirring at room temperature for additional 1 hour. The solvent was evaporated under reduced pressure. The resulting crystal was then washed with diisopropylether and water and was dried under reduced pressure. The dried crystal was purified by silica gel chromatography (eluant:dichloromethane:methanol=10:1) to give (2S,4S)-1-[[N-benzyloxycarbonyl-N-(4-carboxybicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (335 mg).

1. stirringstirring at room temperature for additional 1 hour
2. customThe solvent was evaporated under reduced pressure
3. washThe resulting crystal was then washed with diisopropylether and water
4. customwas dried under reduced pressure
5. customThe dried crystal was purified by silica gel chromatography (eluant:dichloromethane:methanol=10:1)