Dimethylformamide → HCID 67198451, compound

HRID 1423073Notes

Reaction equation

HRID 1423073 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:6]2[CH:7]=[CH:8][N:9]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)[C:10]=2[CH:11]=[C:12](Br)[CH:13]=1)=[O:4].[CH3:22][N:23](C=O)C>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].[C-]#N.[C-]#N.[Zn+2].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].[Zn]>[CH3:1][O:2][C:3]([C:5]1[C:6]2[CH:7]=[CH:8][N:9]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)[C:10]=2[CH:11]=[C:12]([C:22]#[N:23])[CH:13]=1)=[O:4]

Participants

7

Reactant 2

HCID 6228DimethylformamideHCID 67200683HCID 67200683, compound

Product 1

HCID 67198451HCID 67198451, compound

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
120 °C

Procedure

A mixture of 6-bromo-1-(4-fluorophenyl)-1H-indole-4-carboxylic acid methyl ester (1.50 g, 4.30 mmol), Pd2(dba)3 (393.5 mg, 0.43 mmol), Zn(CN)2 (622 mg, 5.30 mmol), dppf (249.48 mg, 0.45 mmol) and Zn (196.11 mg, 3.00 mmol) in DMF (30 mL) is degassed with argon for 5 minutes. The mixture is warmed at 120° C. After 3 hours, the mixture is diluted with saturated aqueous ammonium chloride (30 mL) and extracted with EtOAc. The combined organic layers are washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with EtOAc-hexanes (20:80) to afford 6-cyano-1-(4-fluorophenyl)-1H-indole-4-carboxylic acid methyl ester.

Workup

  1. customis degassed with argon for 5 minutes
  2. additionthe mixture is diluted with saturated aqueous ammonium chloride (30 mL)
  3. extractionextracted with EtOAc
  4. washThe combined organic layers are washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue is purified by silica gel chromatography
  9. washeluting with EtOAc-hexanes (20:80)

Sources & evidence

ORD record
ord-05db304eddac4f8e9a794428d1149814
Source dataset
uspto-grants-2015_01
Patent number
US08927550B2

Reaction notes

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