反应详情

(3S)-Pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester (purchased from Astatech, Inc, 0.5 g, 2.3 mmol) was dissolved in DCM (20 mL) and the solution was cooled to an ice-water bath. To this solution was added a solution of (S)-2-methyl-pyrrolidine (purchased from Advanced Asymmetric, Inc., 235 mg, 2.76 mmol, 1.2 equiv.) in 1 mL of DCM, followed by N-methylmorpholine (700 mg, 6.9 mmol, 3 equiv.) and 1-hydroxylbenzotriazole (HOBT) (404 mg, 3 mmol, 1.3 equiv.) sequentially, and finally EDC.HCl (576 mg, 3 mmol, 1.3 equiv.). The resultant clear light brown solution was stirred at r.t. overnight. TLC (10% MeOH in DCM) and LC/MS detected the product peak at a retention time of 3.238 min with MS 227 (M-t-Bu). The reaction was quenched with aqueous saturated sodium bicarbonate solution (10 mL) and 10 mL of DCM. The two layers were separated, and the aqueous layer was extracted with DCM (15 mL×2). The combined DCM extracts were washed successively with sodium bicarbonate (10 mL) and brine (10 mL), dried (anhydrous potassium carbonate), filtered, and concentrated in vacuum to obtain the title compound, 0.65 g (100% yield), as a thick oil.

1. temperaturethe solution was cooled to an ice-water bath
2. customThe reaction was quenched with aqueous saturated sodium bicarbonate solution (10 mL) and 10 mL of DCM
3. customThe two layers were separated
4. extractionthe aqueous layer was extracted with DCM (15 mL×2)
5. washThe combined DCM extracts were washed successively with sodium bicarbonate (10 mL) and brine (10 mL)
6. dry with materialdried (anhydrous potassium carbonate)
7. filtrationfiltered
8. concentrationconcentrated in vacuum