Acetic Acid → 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

HRID 2065394Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2065394
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]([CH3:23])([CH3:22])[CH3:21])/[C:9]1=[O:24])=O)(C)(C)C.[Cl:25][C:26]1[C:27]([F:39])=[C:28](/[CH:32]=[N:33]/[CH2:34][Si](C)(C)C)[CH:29]=[CH:30][CH:31]=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:24])[C:10]3([CH:18]([CH2:19][C:20]([CH3:22])([CH3:23])[CH3:21])[CH2:34][NH:33][CH:32]3[C:28]3[CH:29]=[CH:30][CH:31]=[C:26]([Cl:25])[C:27]=3[F:39])[C:11]2=[CH:12][CH:13]=1

Komponenten

6

Edukt 4

HCID 176Acetic AcidHCID 962Water2×HCID 58398999(E)-1-(3-chloro-2-fluorophenyl)-N-(trimethylsilylmethyl)methanimineHCID 86656666Z-6-chloro-3-(3,3-dimethyl-butylidene)-2-oxo-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester

Produkt 1

HCID 67336394rac-(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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 12679HexamethylphosphoramideLösungsmittel

Versuchsvorschrift

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%).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-6c81ca81c7904370a76b26ed17d1db44
Quelldatensatz
uspto-grants-2012_10
Patentnummer
US08288431B2

Notizen zur Reaktion

Wird geladen…