反应详情

温度

45 °C

Ethyl 4-aminobicyclo[2.2.2]octane-1-carboxylate hydrochloride (4.63 g), potassium carbonate (5.47 g) and N,N-dimethylformamide (40 mL) were mixed together. To this mixture, a solution of (2S,4S)-1-[2-(benzenesulfonyloxy)acetyl]-4-fluoropyrrolidine-2-carboxamide (5.93 g) in N,N-dimethylformamide (10 mL) was added at 40° C. and the mixture was stirred at 45° C. for 3 hours. Subsequently, the reaction mixture was concentrated under reduced pressure. Water (50 mL) was then added to the residue and the resulting crystal was collected by filtration, washed with water (30 mL), and dried at 50° C. under reduced pressure. The crude crystal was recrystallized from ethyl acetate (40 mL), washed with ethyl acetate (20 mL), and dried at room temperature under reduced pressure. This gave (2S,4S)-1-[2-[(4-ethoxycarbonylbicyclo[2.2.2]oct-1-yl)amino]ac etyl]-4-fluoropyrrolidine-2-carboxamide as a white solid in the form of colorless powder (1.81 g). The filtrate and the wash were combined and concentrated to 20 mL. The resulting crystal was collected by filtration, washed with a mixture of ethyl acetate and diisopropyl ether (1:1, 20 mL) to give additional 1.19 g of the product. The total amount of the product was 3.00 g (45% yield).

1. concentrationSubsequently, the reaction mixture was concentrated under reduced pressure
2. additionWater (50 mL) was then added to the residue
3. filtrationthe resulting crystal was collected by filtration
4. washwashed with water (30 mL)
5. customdried at 50° C. under reduced pressure
6. customThe crude crystal was recrystallized from ethyl acetate (40 mL)
7. washwashed with ethyl acetate (20 mL)
8. customdried at room temperature under reduced pressure
9. concentrationconcentrated to 20 mL
10. filtrationThe resulting crystal was collected by filtration
11. washwashed with a mixture of ethyl acetate and diisopropyl ether (1:1, 20 mL)