1,3-Difluorobenzene → tert-butyl 4-(2,6-difluorobenzoyl)-6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-1H-benzo[d]imidazole-1-carboxylate

HRID 1773683Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1773683
[Li]CCCC.[F:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([F:13])[CH:8]=1.[CH3:14][C:15]1[C:19]([C:20]2[CH:21]=[C:22]([CH:39]=[O:40])[C:23]3[N:27]=[C:26]([O:28][CH2:29][CH3:30])[N:25]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[C:24]=3[CH:38]=2)=[C:18]([CH3:41])[O:17][N:16]=1>C1COCC1>[F:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([F:13])[C:8]=1[C:39]([C:22]1[C:23]2[N:27]=[C:26]([O:28][CH2:29][CH3:30])[N:25]([C:31]([O:33][C:34]([CH3:37])([CH3:35])[CH3:36])=[O:32])[C:24]=2[CH:38]=[C:20]([C:19]2[C:15]([CH3:14])=[N:16][O:17][C:18]=2[CH3:41])[CH:21]=1)=[O:40]

Komponenten

5

Edukt 3

HCID 97411,3-DifluorobenzeneHCID 117601313tert-butyl 6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-4-formyl-1H-benzo[d]imidazole-1-carboxylateHCID 178418339Butyllithium

Produkt 1

HCID 117601789tert-butyl 4-(2,6-difluorobenzoyl)-6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-1H-benzo[d]imidazole-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

n-BuLi (0.58 mL, 0.93 mmol) was added dropwise to a solution of 1,3-difluorobenzene (0.102 mL, 0.1 mmol) in THF (5 mL) cooled to −78° C. and allowed to stir for 1 hour. tert-butyl 6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-4-formyl-1H-benzo[d]imidazole-1-carboxylate (200 mg, 0.52 mmol) in THF was added and the reaction was allowed to stir for 5 mins at −78° C., quenched with ammonium chloride, extracted with EtOAc and concentrated. The crude was then taken up in DCM (2 mL), Des-Martin periodinane (290 mg, 0.78 mmol) was added and the reaction was allowed to stir for 15 mins. The reaction was quenched with sat. Na2S2O3, extracted with EtOAc, concentrated and purified by silica gel chromatography to give tert-butyl 4-(2,6-difluorobenzoyl)-6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-1H-benzo[d]imidazole-1-carboxylate.

Aufarbeitung

  1. stirringto stir for 5 mins at −78° C.
  2. customquenched with ammonium chloride
  3. extractionextracted with EtOAc
  4. concentrationconcentrated
  5. additionDes-Martin periodinane (290 mg, 0.78 mmol) was added
  6. stirringto stir for 15 mins
  7. customThe reaction was quenched with sat. Na2S2O3
  8. extractionextracted with EtOAc
  9. concentrationconcentrated
  10. custompurified by silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-b4b93425df404970b1120659a84e7342
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09255089B2

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