反应详情

To a solution of rac-(2S,3R,4S)-4-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-2-(2,2-dimethyl-propyl)-pyrrolidine-3-carbonitrile (2.5 g, 5.9 mmol) in N,N-dimethylformamide (50 mL) was added tert-butyl bromoacetate (2.5 g, 12.8 mmol) and Cs2CO3 (5 g, 15.4 mmol). The reaction mixture was stirred at room temperature for 66 h. Water was added. The mixture was extracted with ethyl acetate. The organic layer was separated, and aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with water twice, dried over MgSO4, then concentrated. The residue was purified by chromatography (EtOAc:hexanes=1:10) to give rac-[(2S,3R,4S)-4-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-2-(2,2-dimethyl-propyl)-pyrrolidin-1-yl]-acetic acid tert-butyl ester as a white foam (2.1 g, 66%).

1. extractionThe mixture was extracted with ethyl acetate
2. customThe organic layer was separated
3. extractionaqueous layer was extracted with ethyl acetate
4. washwashed with water twice
5. dry with materialdried over MgSO4
6. concentrationconcentrated
7. customThe residue was purified by chromatography (EtOAc:hexanes=1:10)