Dimethylformamide → Methyl 3-amino-4-cyanobenzoate

HRID 746774

Reaction equation

HRID 746774 reaction equation
[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7](Br)=[C:6]([NH2:11])[CH:5]=1.[CH3:13][N:14](C=O)C>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([C:13]#[N:14])=[C:6]([NH2:11])[CH:5]=1

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 3928639Methyl 3-amino-4-bromobenzoate

Product 1

HCID 10261604Methyl 3-amino-4-cyanobenzoateYield 94%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
120 °C

Procedure

Add zinc cyanide (1.5 g, 12.77 mmol), palladium tetrakis (675 mg, 0.584 mmol), to 3-amino-4-bromo-benzoic acid methyl ester (1.328 g, 5.77 mmol) in anhydrous DMF (3 ml). Purge with nitrogen for few minutes and keep under nitrogen atmosphere while heating to 120° C. overnight. Cool the mixture to room temperature and add water. Extract the product with EtOAc (×2). Wash the combined organic layers with 2N ammonium hydroxide solution (×2), water (×2), saturated aq. sodium chloride and dry over anhydrous sodium sulfate, filter and concentrate to yield the crude product. Purification by flash chromatography (Silica gel-hexane/EtOAc) yields 3-amino-4-cyano-benzoic acid methyl ester (94%).

Workup

  1. customPurge with nitrogen for few minutes
  2. temperatureCool the mixture to room temperature
  3. additionadd water
  4. extractionExtract the product with EtOAc (×2)
  5. washWash the combined organic layers with 2N ammonium hydroxide solution (×2), water (×2), saturated aq. sodium chloride
  6. dry with materialdry over anhydrous sodium sulfate
  7. filtrationfilter
  8. concentrationconcentrate
  9. customto yield the crude product
  10. customPurification by flash chromatography (Silica gel-hexane/EtOAc)

Sources & evidence

ORD record
ord-00f200ac29324156975343ac5dc5cd6b
Source dataset
uspto-grants-2008_07
Patent number
US07393868B2

Linked notes

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