2-Bromo-5-fluoropyridine → 2,2-difluoro-2-[4-(5-fluoropyridin-2-yl)phenyl]-N-methoxy-N-methylacetamide

HRID 216416

Reaktionsgleichung

Reaktionsgleichung von HRID 216416
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:16])([F:15])[C:9]([N:11]([O:13][CH3:14])[CH3:12])=[O:10])=[CH:4][CH:3]=1.Br[C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][N:19]=1.C[Sn](C)C.C[Sn](C)C>O1CCOCC1.O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[F:15][C:8]([F:16])([C:5]1[CH:6]=[CH:7][C:2]([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][N:19]=2)=[CH:3][CH:4]=1)[C:9]([N:11]([O:13][CH3:14])[CH3:12])=[O:10]

Komponenten

7

Edukt 3

HCID 27831712-Bromo-5-fluoropyridineHCID 6327618HexamethylditinHCID 866385182-(4-bromophenyl)-2,2-difluoro-N-methoxy-N-methylacetamide

Produkt 1

HCID 866385172,2-difluoro-2-[4-(5-fluoropyridin-2-yl)phenyl]-N-methoxy-N-methylacetamide

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumKatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

Palladium tetrakis(triphenylphosphine) (236 mg, 0.20 mmol) was added to a degassed, ambient temperature solution of 2-(4-bromophenyl)-2,2-difluoro-N-methoxy-N-methylacetamide (600 mg, 2.05 mmol), 2-bromo-5-fluoropyridine (360 mg, 2.05 mmol) and hexamethylditin (670 mg, 2.05 mmol) in 1,4-dioxane (20 mL). After stirring at reflux overnight, the reaction mixture was diluted with water and extracted with methylene chloride and ethyl acetate. The combined organic extracts were dried (magnesium sulfate) and concentrated in vacuo. Chromatography over silica eluting with 0-60% ethyl acetate/hexane afforded 2,2-difluoro-2-[4-(5-fluoropyridin-2-yl)phenyl]-N-methoxy-N-methylacetamide.

Aufarbeitung

  1. temperatureat reflux overnight
  2. extractionextracted with methylene chloride and ethyl acetate
  3. dry with materialThe combined organic extracts were dried (magnesium sulfate)
  4. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-1b70c91b52474c9d99a038ea40fafc7f
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08193228B2

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