反应详情

温度

0 °C

Under a nitrogen atmosphere, 60% sodium hydride (0.149 g, 3.73 mmol) was suspended in anhydrous tetrahydrofuran (20 ml) to which, after cooling to 0° C., was subsequently added dropwise a dry tetrahydrofuran (20 ml) solution of 1-benzyloxycarbonyl-3-(S)-hydroxy-4-(R)-(1-ethoxycarbonylcyclopropyl)pyrrolidine (0.98 g, 2.92 mmol) over a period of 5 minutes. After 15 minutes of stirring in an ice bath, dimethyl sulfate (0.441 ml, 4.66 mmol) was added dropwise to the-reaction solution which was cooled in the ice bath. The reaction solution was stirred at room temperature for 4 hours and then mixed with water (0.5 ml), followed by evaporating tetrahydrofuran under reduced pressure. The thus obtained residue was dissolved in ethanol (40 ml), and a 1 M sodium hydroxide aqueous solution (8.76 ml) was added dropwise to the resulting solution at room temperature. The reaction'solution was heated under reflux for 2 hours and then ethanol was evaporated under reduced pressure. The resulting residue was cooled in an ice bath, acidified by adding dropwise a 1 M hydrochloric acid aqueous solution (15 ml) and then extracted with ethyl acetate (50 ml×3). All of the organic layers were combined, washed with a 1 N hydrochloric acid aqueous solution (50 ml) and saturated brine (50 ml) and then dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure to obtain 0.935 g (quantitative) of the title compound as a colorless amorphous substance.

1. stirringThe reaction solution was stirred at room temperature for 4 hours
2. customby evaporating tetrahydrofuran under reduced pressure
3. dissolutionThe thus obtained residue was dissolved in ethanol (40 ml)
4. additiona 1 M sodium hydroxide aqueous solution (8.76 ml) was added dropwise to the resulting solution at room temperature
5. temperatureThe reaction'solution was heated
6. temperatureunder reflux for 2 hours
7. customethanol was evaporated under reduced pressure
8. temperatureThe resulting residue was cooled in an ice bath
9. additionby adding dropwise a 1 M hydrochloric acid aqueous solution (15 ml)
10. extractionextracted with ethyl acetate (50 ml×3)
11. washwashed with a 1 N hydrochloric acid aqueous solution (50 ml) and saturated brine (50 ml)
12. dry with materialdried over anhydrous sodium sulfate
13. filtrationAfter filtration
14. concentrationthe filtrate was concentrated under reduced pressure