Ethyl Acetate → 5-formylthiophene-3-carbonitrile

HRID 1071620Notes

Reaction equation

HRID 1071620 reaction equation
CO[CH:3]([O:10]C)[C:4]1[S:5][CH:6]=[C:7](Br)[CH:8]=1.[Cu](C#N)[C:13]#[N:14].C(OCC)(=O)C>CN(C=O)C.C(O)(=O)C>[C:13]([C:7]1[CH:8]=[C:4]([CH:3]=[O:10])[S:5][CH:6]=1)#[N:14]

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 22393566HCID 22393566, compoundHCID 178418260HCID 178418260, compound

Product 1

HCID 122800095-formylthiophene-3-carbonitrileYield 62%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

4-Bromo-2-thiophenecarboaldehyde dimethylacetal (6.82 g) was dissolved in DMF (50 ml), and copper cyanide (4.29 g) was added thereto. After heating under reflux for 3 hours, the mixture was cooled as it was to room temperature and ethyl acetate was added thereto. The mixture was washed with an aqueous ammonia, water, 0.1N aqueous hydrochloric acid and brine, dried over anhydrous magnesium sulfate and then evaporated, to give an oil. The residue was dissolved in an 80% aqueous acetic acid (100 ml), and the mixture was stirred at 0° C. for one hour. The mixture was washed with brine. After cooling as it was to room temperature, ethyl acetate was added thereto. The mixture was washed with an aqueous saturated sodium bicarbonate and brine, dried over anhydrous magnesium sulfate and then evaporated. The resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate system), and then recrystallized from ethyl acetate-hexane, to give the title compound as pale yellowish white crystals (2.44 g, 62%).

Workup

  1. temperatureAfter heating
  2. temperatureunder reflux for 3 hours
  3. temperaturethe mixture was cooled as it
  4. customwas to room temperature
  5. washThe mixture was washed with an aqueous ammonia, water, 0.1N aqueous hydrochloric acid and brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customevaporated
  8. customto give an oil
  9. washThe mixture was washed with brine
  10. temperatureAfter cooling as it
  11. customwas to room temperature
  12. additionethyl acetate was added
  13. washThe mixture was washed with an aqueous saturated sodium bicarbonate and brine
  14. dry with materialdried over anhydrous magnesium sulfate
  15. customevaporated
  16. customThe resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate system)
  17. customrecrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-c889159daf804e1a8b599bd1553cb88d
Source dataset
uspto-grants-2005_06
Patent number
US06906072B1

Reaction notes

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