Chlorosuccinimide → (1S,2S)-1-[4-chloro-5-(2-fluoro-4-iodo-phenyl)-1H-imidazol-2-yl]-2-phenyl-propylamine

HRID 561964Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 561964
C(OC(=O)[NH:7][C@H:8]([C:17]1[NH:18][C:19]([C:22]2[CH:27]=[CH:26][C:25]([I:28])=[CH:24][C:23]=2[F:29])=[CH:20][N:21]=1)[C@H:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH3:10])(C)(C)C.[Cl:31]N1C(=O)CCC1=O>C(#N)C.O1CCCC1>[Cl:31][C:20]1[N:21]=[C:17]([C@@H:8]([NH2:7])[C@H:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH3:10])[NH:18][C:19]=1[C:22]1[CH:27]=[CH:26][C:25]([I:28])=[CH:24][C:23]=1[F:29]

Komponenten

4

Edukt 2

HCID 31398ChlorosuccinimideHCID 67001487{(1S,2S)-1-[5-(2-fluoro-4-iodo-phenyl)-1H-imidazol-2-yl]-2-phenyl-propyl}-carbamic acid tert-butyl ester

Produkt 1

HCID 178461664(1S,2S)-1-[4-chloro-5-(2-fluoro-4-iodo-phenyl)-1H-imidazol-2-yl]-2-phenyl-propylamine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 22177404Acetonitrile tetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of {(1S,2S)-1-[5-(2-fluoro-4-iodo-phenyl)-1H-imidazol-2-yl]-2-phenyl-propyl}-carbamic acid tert-butyl ester (1.10 g, 2.11 mmol) in 10:1 v/v acetonitrile/tetrahydrofuran (20 mL) under an atmosphere of nitrogen was added N-chlorosuccinimide (352 mg, 2.64 mmol) and the mixture was refluxed for 24 hours. The reaction was concentrated in vacuo, diluted with ethyl acetate (60 mL) and washed with saturated sodium hydrogen carbonate solution. The organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. To a solution of the crude product in dichloromethane (20 mL) under an atmosphere of nitrogen was added trifluoroacetic acid (6 mL) and the mixture was stirred for one hour. The reaction mixture was concentrated in vacuo then basified with saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate (2×50 mL). The organic extracts were combined, washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to give (1S,2S)-1-[4-chloro-5-(2-fluoro-4-iodo-phenyl)-1H-imidazol-2-yl]-2-phenyl-propylamine which was used in the subsequent step without further purification (860 mg, 89%).

Aufarbeitung

  1. temperaturethe mixture was refluxed for 24 hours
  2. concentrationThe reaction was concentrated in vacuo
  3. additiondiluted with ethyl acetate (60 mL)
  4. washwashed with saturated sodium hydrogen carbonate solution
  5. washThe organic layer was washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. additionTo a solution of the crude product in dichloromethane (20 mL) under an atmosphere of nitrogen was added trifluoroacetic acid (6 mL)
  10. concentrationThe reaction mixture was concentrated in vacuo
  11. extractionextracted with ethyl acetate (2×50 mL)
  12. washwashed with brine
  13. dry with materialdried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-91552d4ab3994f8c836b288d553be76f
Quelldatensatz
uspto-grants-2011_11
Patentnummer
US08063085B2

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