C(OC([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([Cl:17])[CH:15]=2)/[C:10](=[CH:18]/[CH2:19][C:20]([CH3:31])([CH3:30])[CH2:21][O:22][Si](C(C)(C)C)(C)C)/[C:9]1=[O:32])=O)(C)(C)C.[Cl:33][C:34]1[C:35]([F:47])=[C:36](/[CH:40]=[N:41]/[CH2:42][Si](C)(C)C)[CH:37]=[CH:38][CH:39]=1.C(O)(=O)C.O>CN(C)P(N(C)C)(N(C)C)=O>[Cl:17][C:14]1[CH:15]=[C:16]2[NH:8][C:9](=[O:32])[C:10]3([CH:18]([CH2:19][C:20]([CH3:30])([CH3:31])[CH2:21][OH:22])[CH2:42][NH:41][CH:40]3[C:36]3[CH:37]=[CH:38][CH:39]=[C:34]([Cl:33])[C:35]=3[F:47])[C:11]2=[CH:12][CH:13]=1To a solution of E/Z-3-[4-(tert-butyl-dimethyl-silanyloxy)-3,3-dimethyl-butylidene]-6-chloro-2-oxo-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester prepared in Example 31 (2.5 g, 5.2 mmol) in hexamethylphosphoramide (30 mL) was added [1-(3-chloro-2-fluoro-phenyl)-meth-(E)-ylidene]-trimethylsilanylmethyl-amine prepared in Example 5 (2.9 g, 12 mmol), acetic acid (0.75 g, 12 mmol) and H2O (0.25 g, 14 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 (10 mL), and trifluoroacetic acid (5 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 dissolved into tetrahydrofuran (5 mL), and saturated aqueous NaHCO3 solution was added (5 mL). The reaction mixture was stirred at room temperature for 1 h. The mixture was concentrated, and the residue was partitioned between ethyl acetate and water. The organic layer was separated, dried over MgSO4, then concentrated. The residue was purified by chromatography (3% MeOH in EtOAc) to give rac-(2′S,3′S,4′S)-6-chloro-2′-(3-chloro-2-fluoro-phenyl)-4′-(3-hydroxy-2,2-dimethyl-propyl)-1H-spiro[indole-3,3′-pyrrolidin]-2-one as a white solid (Yield, 0.25 g, 11%).
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