反应详情

温度

85 °C

With cooling with ice, methanesulfonyl chloride (923 μl, 11.9 mmol) and triethylamine (1.94 ml, 13.9 mmol) were added to a dichloromethane (100 ml) solution of tert-butyl (2S)-2-(hydroxymethyl)pyrrolidine-1-carboxylate (2.00 g, 9.94 mmol), followed by stirring for 30 minutes with cooling with ice. The reaction liquid was concentrated under reduced pressure, dissolved in ethyl acetate, and washed with saturated brine. After drying over anhydrous sodium sulfate, the insoluble matter was separated by filtration, and the residue obtained by concentration was dissolved in acetone (50 ml), then sodium iodide (1.49 g, 9.94 mmol) was added, followed by heating under reflux in an oil bath at 85° C. for 5 hours. The reaction liquid was concentrated under reduced pressure, the residue was suspended in ethyl acetate, washed with water and saturated brine. After drying over anhydrous sodium sulfate, the insoluble matter was separated by filtration, the residue obtained by concentration was dissolved in dimethylformamide (30 ml), then dimethylamine hydrochloride (2.43 g, 29.8 mmol) and potassium carbonate (2.75 g, 19.9 mmol) were added, followed by stirring at room temperature for 24 hours. The reaction liquid was concentrated under reduced pressure, the residue was suspended in ethyl acetate, and washed with water and saturated brine. After drying over anhydrous sodium sulfate and concentration, the resulting residue was purified by silica gel column chromatography (eluent, chloroform:methanol=10:1, v/v) to obtain the entitled compound (92.0 mg, 4%) as a colorless oily substance.

1. temperaturewith cooling with ice
2. customThe reaction liquid
3. concentrationwas concentrated under reduced pressure
4. dissolutiondissolved in ethyl acetate
5. washwashed with saturated brine
6. dry with materialAfter drying over anhydrous sodium sulfate
7. customthe insoluble matter was separated by filtration
8. customthe residue obtained by concentration
9. temperatureby heating
10. customThe reaction liquid
11. concentrationwas concentrated under reduced pressure
12. washwashed with water and saturated brine
13. dry with materialAfter drying over anhydrous sodium sulfate
14. customthe insoluble matter was separated by filtration
15. customthe residue obtained by concentration
16. stirringby stirring at room temperature for 24 hours
17. customThe reaction liquid
18. concentrationwas concentrated under reduced pressure
19. washwashed with water and saturated brine
20. dry with materialAfter drying over anhydrous sodium sulfate and concentration
21. customthe resulting residue was purified by silica gel column chromatography (eluent, chloroform