反应详情

To a solution of E/Z-6-chloro-3-(3,3-dimethyl-butylidene)-2-oxo-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester prepared in Example 4 (2.5 g, 7.1 mmol) in hexamethylphosphoramide (30 mL) was added [1-(3-chloro-2-fluoro-phenyl)-meth-(E)-ylidene]-trimethylsilanylmethyl-amine prepared in Example 5 (2.4 g, 9.9 mmol), acetic acid (0.6 g, 10 mmol) and H2O (0.2 g, 11 mmol) sequentially. The reaction mixture was stirred at room temperature for 24 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 dissolved into dichloromethane (20 mL), and trifluoroacetic acid (10 mL) was added. The reaction mixture was stirred at room temperature for 1 h. The mixture was concentrated, and the residue was partitioned between ethyl acetate and aqueous saturated NaHCO3 solution. The organic layer was separated, dried over MgSO4, then concentrated. The residue was purified by chromatography (50-100% EtOAc in hexanes) to give rac-(2′S,3′S,4′S)-6-chloro-2′-(3-chloro-2-fluoro-phenyl)-4′-(2,2-dimethyl-propyl)-1H-spiro[indole-3,3′-pyrrolidin]-2-one as a white solid (Yield, 0.6 g, 20%).

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. dissolutionThe residue was dissolved into dichloromethane (20 mL), and trifluoroacetic acid (10 mL)
8. additionwas added
9. stirringThe reaction mixture was stirred at room temperature for 1 h
10. concentrationThe mixture was concentrated
11. customthe residue was partitioned between ethyl acetate and aqueous saturated NaHCO3 solution
12. customThe organic layer was separated
13. dry with materialdried over MgSO4
14. concentrationconcentrated
15. customThe residue was purified by chromatography (50-100% EtOAc in hexanes)
16. customto give