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

HRID 216416Notes

Reaction equation

HRID 216416 reaction equation
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]

Participants

7

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-1b70c91b52474c9d99a038ea40fafc7f
Source dataset
uspto-grants-2012_06
Patent number
US08193228B2

Reaction notes

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