Water → 3-Fluoro-4-formylbenzonitrile

HRID 2361912Notes

Reaction equation

HRID 2361912 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[CH3:10])[C:5]#[N:6].C[O:12]C(OC)N(C)C.O.I([O-])(=O)(=O)=O.[Na+]>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[CH:10]=[O:12])[C:5]#[N:6]

Participants

6

Reactant 4

HCID 962WaterHCID 78373Dimethylformamide dimethyl acetalHCID 5851403-Fluoro-4-methylbenzonitrileHCID 23667635Sodium periodate

Product 1

HCID 27831503-Fluoro-4-formylbenzonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The reaction was carried out under argon. 3-Fluoro-4-methylbenzonitrile (121 g, 895 mmol) and N,N-dimethylformamide dimethylacetal (245 g, 2.06 mol) were dissolved in DMF (1.8 liters) and stirred under reflux overnight. The content of the flask was then poured into water (2 liters), the mixture was extracted twice with ethyl acetate and the combined organic phases were washed with saturated sodium chloride solution. The organic phase was concentrated and the residue was redissolved in THF/water (1:1, 2.7 liters). Sodium periodate (503 g, 2.35 mol) was added, and the mixture was stirred at room temperature for one hour. The precipitate was then removed and the filtrate was recovered and extracted repeatedly with ethyl acetate. The combined organic phases were washed once with saturated sodium bicarbonate solution and once with saturated sodium chloride solution, dried and concentrated to give an oil. This oil was purified by column chromatography on silica gel (mobile phase: petroleum ether/dichloromethane 6:4, then 4:6, finally pure dichloromethane). The product fractions were concentrated. This gave 28.0 g (20% of theory) of the target compound as a white crystalline solid.

Workup

  1. temperatureunder reflux overnight
  2. extractionthe mixture was extracted twice with ethyl acetate
  3. washthe combined organic phases were washed with saturated sodium chloride solution
  4. concentrationThe organic phase was concentrated
  5. dissolutionthe residue was redissolved in THF/water (1:1, 2.7 liters)
  6. stirringthe mixture was stirred at room temperature for one hour
  7. customThe precipitate was then removed
  8. customthe filtrate was recovered
  9. extractionextracted repeatedly with ethyl acetate
  10. washThe combined organic phases were washed once with saturated sodium bicarbonate solution and once with saturated sodium chloride solution
  11. customdried
  12. concentrationconcentrated
  13. customto give an oil
  14. customThis oil was purified by column chromatography on silica gel (mobile phase
  15. concentrationThe product fractions were concentrated

Sources & evidence

ORD record
ord-464a780c97ab48c996f61e7ec19e69b4
Source dataset
uspto-grants-2014_04
Patent number
US08691817B2

Reaction notes

Loading…