反应详情

Methyl (2S,4R)-4-hydroxypyrrolidine-2-carboxylate 3a (5.53 g, 38 mmol) was dissolved in 80 mL of methanol in an ice-water bath, followed by addition of 40% formaldehyde solution (31 mL, 380 mmol) and sodium cyanoborohydride (12 g, 190 mmol) in batches. The reaction mixture was stirred for 0.5 hours, then warmed up to room temperature and stirred for 3 hours. The mixture was quenched with 40 mL of water, concentrated under reduced pressure and extracted with dichloromethane (80 mL×3). The combined organic extracts were washed with saturated brine (30 mL×2), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to obtain the title compound methyl (2S,4R)-4-hydroxy-1-methyl-pyrrolidine-2-carboxylate 3b crude product as a colourless oil, which was directly used in the next step.

1. stirringstirred for 3 hours
2. customThe mixture was quenched with 40 mL of water
3. concentrationconcentrated under reduced pressure
4. extractionextracted with dichloromethane (80 mL×3)
5. washThe combined organic extracts were washed with saturated brine (30 mL×2)
6. dry with materialdried over anhydrous sodium sulfate
7. filtrationfiltered
8. concentrationThe filtrate was concentrated under reduced pressure