Sodium Carbonate → Methyl 3-cyano-4-hydroxybenzoate

HRID 2192478Notes

Reaction equation

HRID 2192478 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[OH:12])[C:5]([O:7][CH3:8])=[O:6].C(=O)([O-])[O-].[Na+].[Na+].[CH3:19][N:20](C)C(=O)C>O.O.O.[Fe-4](C#N)(C#N)(C#N)(C#N)(C#N)C#N.[K+].[K+].[K+].[K+].C([O-])(=O)C.[Pd+2].C([O-])(=O)C.[CH-]1C(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=C1.[CH-]1C(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=C1.[Fe+2]>[C:19]([C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[OH:12])[C:5]([O:7][CH3:8])=[O:6])#[N:20]

Participants

8

Reactant 3

HCID 10340Sodium Carbonate2×HCID 31374DimethylacetamideHCID 4778958Methyl 3-bromo-4-hydroxybenzoate

Product 1

HCID 11769089Methyl 3-cyano-4-hydroxybenzoate

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalyst2×HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 152416121,1`-Bis(diphenylphosphino)ferroceneCatalystHCID 178511497HCID 178511497, compoundCatalyst

Procedure

A mixture of methyl 3-bromo-4-hydroxybenzoate (Journal of Organic Chemistry (1997), 62(13), 4504-4506; 3.47 g, 15.0 mmol), potassium ferrocyanide trihydrate (1.394 g, 3.30 mmol), palladium acetate (0.034 g, 0.150 mmol), 1,1-bis(diphenylphosphino)ferrocene (0.166 g, 0.300 mmol), and sodium carbonate (1.590 g, 15.00 mmol) in dry N,N-dimethylacetamide (DMA) (30 ml) was degassed by evacuation and refilling with nitrogen, and the mixture was heated under nitrogen at 125° for 18 h. More potassium ferrocyanide trihydrate (700 mg), palladium acetate (34 mg) and 1,1′-bis(diphenylphosphino)ferrocene (166 mg) were added, and stirring was continued under nitrogen at 130° for 21.5 h. More sodium carbonate (1.59 g), palladium acetate (0.034 g, 0.150 mmol) and 1,1′-bis(diphenylphosphino)ferrocene (0.166 g, 0.300 mmol) was added, and heating was continued at 130° with stirring under nitrogen for 4 h. The solvent was evaporated in vacuo and the residue treated with glacial acetic acid (3 ml) and partitioned between water (100 ml) and ethyl acetate (100 ml). The layers separated poorly, hence the mixture was filtered through Celite filter aid, and the aqueous layer was further extracted with ethyl acetate (70 ml). The combined organic layers were washed with saturated aqueous sodium chloride, dried (MgSO4) and evaporated in vacuo to give a black solid which was purified by flash chromatography on silica, eluting with 0-50% ethyl acetate-cyclohexane. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a yellow solid (1.01 g)

Workup

  1. customwas degassed by evacuation and refilling with nitrogen
  2. temperaturethe mixture was heated under nitrogen at 125° for 18 h
  3. additionMore potassium ferrocyanide trihydrate (700 mg), palladium acetate (34 mg) and 1,1′-bis(diphenylphosphino)ferrocene (166 mg) were added
  4. temperatureheating
  5. customwas continued at 130°
  6. stirringwith stirring under nitrogen for 4 h
  7. customThe solvent was evaporated in vacuo
  8. additionthe residue treated with glacial acetic acid (3 ml)
  9. custompartitioned between water (100 ml) and ethyl acetate (100 ml)
  10. customThe layers separated poorly
  11. filtrationhence the mixture was filtered through Celite
  12. filtrationfilter aid
  13. extractionthe aqueous layer was further extracted with ethyl acetate (70 ml)
  14. washThe combined organic layers were washed with saturated aqueous sodium chloride
  15. dry with materialdried (MgSO4)
  16. customevaporated in vacuo
  17. customto give a black solid which
  18. customwas purified by flash chromatography on silica
  19. washeluting with 0-50% ethyl acetate-cyclohexane
  20. customevaporated in vacuo

Sources & evidence

ORD record
ord-8bbb02db3dd047cb85f139e8c74c1b93
Source dataset
uspto-grants-2012_12
Patent number
US08329730B2

Reaction notes

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