反应详情

To a stirred solution of pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 35 (10 g, 46.46 mmol) in dry THF were added drop wise N-methyl morpholine (6.4 mL, 58.1 mmol) and isobutyl chloroformate (6.7 mL, 65.1 mmol) at −30° C. The reaction mixture was stirred at same temperature for one hour and diazomethane solution (prepared in situ) was added at −30° C. The resulting mixture was allowed to stir at rt overnight. Excess diazomethane was quenched with acetic acid (15 mL) and evaporated under reduced pressure. The residue was dissolved in ether and washed with water and brine. The organic layer was dried over anhydrous Na2SO4, filtered and evaporated. The residue was dissolved in methanol (100 mL) and Ag2O (5.5 g) was added portion-wise at ice-cold conditions, and then allowed to stir at rt for 2 hours. Chloroform was added, filtered through Celite® reagent and washed with methanol. The filtrate was concentrated and the crude material was purified by chromatography on silica-gel (230-400 mesh) eluting with 1-5% of ethyl acetate-hexane to get light yellow liquid compound 36.

1. stirringto stir at rt overnight
2. customExcess diazomethane was quenched with acetic acid (15 mL)
3. customevaporated under reduced pressure
4. dissolutionThe residue was dissolved in ether
5. washwashed with water and brine
6. dry with materialThe organic layer was dried over anhydrous Na2SO4
7. filtrationfiltered
8. customevaporated
9. dissolutionThe residue was dissolved in methanol (100 mL)
10. additionAg2O (5.5 g) was added portion-wise at ice-cold conditions
11. stirringto stir at rt for 2 hours
12. additionChloroform was added
13. filtrationfiltered through Celite® reagent
14. washwashed with methanol
15. concentrationThe filtrate was concentrated
16. customthe crude material was purified by chromatography on silica-gel (230-400 mesh)
17. washeluting with 1-5% of ethyl acetate-hexane