反应详情

2-Tetrahydropyranyl 4-aminobicyclo[2.2.2]octane-1-carboxylate (62.9 mg) was suspended in acetonitrile (1 mL). To this solution, diisopropylethylamine (47 μL) was added and (2S,4S)-1-(2-bromoacetyl)-4-fluoropyrrolidine-2-carbonitrile (53.1 mg) in acetonitrile (0.8 mL) was added while the mixture was chilled in an ice bath. The mixture was stirred for 4 hours and concentrated. To the resulting residue, ethyl acetate and water were added, followed by an aqueous sodium bicarbonate solution to make the pH basic. The solution was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (eluant:dichloromethane:methanol=10:1) to give (2S,4S)-1-[[N-[4-(2-tetrahydropyranyl)oxycarbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (73.3 mg).

1. temperaturewas chilled in an ice bath
2. concentrationconcentrated
3. additionTo the resulting residue, ethyl acetate and water were added
4. extractionThe solution was extracted with ethyl acetate
5. washThe ethyl acetate layer was washed with saturated brine
6. dry with materialdried over anhydrous sodium sulfate
7. concentrationconcentrated under reduced pressure
8. customThe resulting residue was purified by silica gel chromatography (eluant:dichloromethane:methanol=10:1)