Potassium Carbonate → N-(2,2-difluoroethyl)-6-((2R,6R)-2,6-dimethylmorpholino)-7-fluoro-5-formylbenzo[d]isoxazole-3-carboxamide

HRID 577943Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 577943
[F:1][CH:2]([F:20])[CH2:3][NH:4][C:5]([C:7]1[C:11]2[CH:12]=[C:13]([CH:18]=[O:19])[C:14](F)=[C:15]([F:16])[C:10]=2[O:9][N:8]=1)=[O:6].C(=O)([O-])[O-].[K+].[K+].[CH3:27][C@H:28]1[O:33][C@H:32]([CH3:34])[CH2:31][NH:30][CH2:29]1>C(#N)CCC.O.[Cl-].[Na+].O.C(OCC)(=O)C>[F:1][CH:2]([F:20])[CH2:3][NH:4][C:5]([C:7]1[C:11]2[CH:12]=[C:13]([CH:18]=[O:19])[C:14]([N:30]3[CH2:29][C@@H:28]([CH3:27])[O:33][C@H:32]([CH3:34])[CH2:31]3)=[C:15]([F:16])[C:10]=2[O:9][N:8]=1)=[O:6]

Komponenten

8

Edukt 3

HCID 11430Potassium CarbonateHCID 11137133trans-2,6-DimethylmorpholineHCID 86658102N-(2,2-Difluoroethyl)-6,7-difluoro-5-formylbenzo[d]isoxazole-3-carboxamide2×

Produkt 1

HCID 86658101N-(2,2-difluoroethyl)-6-((2R,6R)-2,6-dimethylmorpholino)-7-fluoro-5-formylbenzo[d]isoxazole-3-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 962WaterLösungsmittel2×HCID 8008ButyronitrileLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 57417360Sodium chloride; waterLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

N-(2,2-Difluoroethyl)-6,7-difluoro-5-formylbenzo[d]isoxazole-3-carboxamide (Intermediate 243, 2.86 g, 9.86 mmol) was dissolved in butyronitrile (50 mL) and water (2.5 mL). Potassium carbonate (1.362 g, 9.86 mmol) and (2R,6R)-2,6-dimethylmorpholine (1.481 mL, 11.83 mmol) were added and the reaction was stirred at 90° C. for 4 hours. The crude reaction mixture was diluted with water, brine and ethyl acetate. The mixture was washed 2× with brine. The aqueous layer was back-extracted with ethyl acetate. The organic layers combined, dried over MgSO4 and concentrated. The residue was dissolved in DCM and purified by silica gel column chromatography using a gradient of DCM to ethyl acetate. Fractions were combined and concentrated to give the title compound.

Aufarbeitung

  1. customThe crude reaction mixture
  2. washThe mixture was washed 2× with brine
  3. extractionThe aqueous layer was back-extracted with ethyl acetate
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved in DCM
  7. custompurified by silica gel column chromatography
  8. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-7478b0cfc43d4f799e09f27716242dae
Quelldatensatz
uspto-grants-2015_05
Patentnummer
US09040528B2

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