Water → 3-{1-[(3-fluorophenyl)sulfonyl]-4-formyl-1H-pyrrol-2-yl}pyridine-2-carbonitrile

HRID 1426668Notes

Reaction equation

HRID 1426668 reaction equation
Cl[C:2]1[C:7]([C:8]2[N:12]([S:13]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=3)(=[O:15])=[O:14])[CH:11]=[C:10]([CH:23]=[O:24])[CH:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.[Cu][C:26]#[N:27].O.C(OCC)(=O)C>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[F:22][C:18]1[CH:17]=[C:16]([S:13]([N:12]2[CH:11]=[C:10]([CH:23]=[O:24])[CH:9]=[C:8]2[C:7]2[C:2]([C:26]#[N:27])=[N:3][CH:4]=[CH:5][CH:6]=2)(=[O:15])=[O:14])[CH:21]=[CH:20][CH:19]=1

Participants

8

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 866239845-(2-chloropyridin-3-yl)-1-[(3-fluorophenyl)sulfonyl]-1H-pyrrole-3-carbaldehydeHCID 178418546HCID 178418546, compound2×

Product 1

HCID 866239853-{1-[(3-fluorophenyl)sulfonyl]-4-formyl-1H-pyrrol-2-yl}pyridine-2-carbonitrileYield 17.1%

Reagents, catalysts & solvents 3

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)Catalyst2×HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 312751,4-DioxaneSolvent

Procedure

5-(2-Chloropyridin-3-yl)-1-[(3-fluorophenyl)sulfonyl]-1H-pyrrole-3-carbaldehyde (420 mg), copper (I) cyanide (516 mg), tris(dibenzylideneacetone)dipalladium (0) (53 mg) and 1,1′-bis(diphenylphosphino)ferrocene (96 mg) were mixed in 1,4-dioxane (20 mL), and the mixture was heated under reflux for 3 hr. The reaction mixture was cooled to around room temperature, copper (I) cyanide (516 mg), tris(dibenzylideneacetone)dipalladium (0) (53 mg) and 1,1′-bis(diphenylphosphino)ferrocene (96 mg) were added and the mixture was heated under reflux for 60 hr. The reaction mixture was allowed to cool, water and ethyl acetate were added and the mixture was filtered. The obtained ethyl acetate layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=7:3→3:2) to give the title compound as a colorless oil (yield 70 mg, 17%).

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 3 hr
  3. temperatureThe reaction mixture was cooled to around room temperature
  4. temperaturethe mixture was heated
  5. temperatureunder reflux for 60 hr
  6. temperatureto cool
  7. filtrationthe mixture was filtered
  8. washThe obtained ethyl acetate layer was washed with saturated brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=7:3→3:2)

Sources & evidence

ORD record
ord-38541447bb24477b8aa332a180f5add9
Source dataset
uspto-grants-2015_01
Patent number
US08933105B2

Reaction notes

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