Water → 3-Fluoro-4-formylbenzonitrile

HRID 336894

Reaction equation

HRID 336894 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 dimethyl acetal (245 g, 2.06 mol) were dissolved in DMF (1.8 liters) and stirred under reflux overnight. The contents 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 dissolved again 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 separated off, 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 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 dissolved again in THF/water (1:1, 2.7 liters)
  6. stirringthe mixture was stirred at room temperature for one hour
  7. customThe precipitate was then separated off
  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 was purified by column chromatography on silica gel (mobile phase
  15. concentrationThe product fractions were concentrated

Sources & evidence

ORD record
ord-bf1433938c5e4b26ad4981e470e07e56
Source dataset
uspto-grants-2014_11
Patent number
US08889700B2

Linked notes

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