O-Xylene → 1-(4-Fluorophenyl)-4-oxocyclohexanecarbonitrile

HRID 359401

Reaction equation

HRID 359401 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]#[N:10])=[CH:4][CH:3]=1.C[O-].[Na+].[C:14]([O:18]C)(=O)[CH:15]=[CH2:16].[CH3:20][C:21]1C=CC=CC=1C>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:9]#[N:10])[CH2:16][CH2:15][C:14](=[O:18])[CH2:21][CH2:20]2)=[CH:4][CH:3]=1

Participants

5

Reactant 4

HCID 7237O-XyleneHCID 7294Methyl AcrylateHCID 68016Benzeneacetonitrile, 4-fluoro-HCID 10942334Sodium Methoxide

Product 1

HCID 918051-(4-Fluorophenyl)-4-oxocyclohexanecarbonitrile

Procedure

A mixture of 221 parts of 4-fluorobenzeneacetonitrile, 700 parts of sodium methoxide solution 30% and 900 parts of dimethylbenzene was stirred for 5 minutes. Then there were added dropwise 309 parts of methyl 2-propenoate (exothermic reaction: temperature rose to 65° C.). Upon completion, stirring was continued overnight at reflux temperature. The methanol was distilled off till an internal temperature of 110° C. was reached. After cooling, 1000 parts of a hydrochloric acid solution 6N were added dropwise and the whole was stirred and refluxed for 5 minutes. Upon cooling, the layers were separated. The organic phase was dried, filtered and evaporated. The residue was stirred and refluxed for 4 hours together with 500 parts of acetic acid, 500 parts of water and 500 parts of a hydrochloric acid solution. After cooling, the product was extracted with trichloromethane. The extract was washed successively with water, with a diluted sodium hydroxide solution and again with water till neutralization, dried, filtered and evaporated. The residue was crystallized from 2-propanol, yielding 134.5 parts of 1-(4-fluorophenyl)-4-oxocyclohexanecarbonitrile; mp. 91.8° C. (intermediate 1).

Workup

  1. stirringUpon completion, stirring
  2. waitwas continued overnight
  3. temperatureat reflux temperature
  4. distillationThe methanol was distilled off till an internal temperature of 110° C.
  5. temperatureAfter cooling
  6. addition1000 parts of a hydrochloric acid solution 6N were added dropwise
  7. stirringthe whole was stirred
  8. temperaturerefluxed for 5 minutes
  9. temperatureUpon cooling
  10. customthe layers were separated
  11. customThe organic phase was dried
  12. filtrationfiltered
  13. customevaporated
  14. stirringThe residue was stirred
  15. temperaturerefluxed for 4 hours together with 500 parts of acetic acid, 500 parts of water and 500 parts of a hydrochloric acid solution
  16. temperatureAfter cooling
  17. extractionthe product was extracted with trichloromethane
  18. washThe extract was washed successively with water, with a diluted sodium hydroxide solution and again with water till neutralization,
  19. customdried
  20. filtrationfiltered
  21. customevaporated
  22. customThe residue was crystallized from 2-propanol

Sources & evidence

ORD record
ord-f87bb568ddf449ee9d83b9b9813a5e7b
Source dataset
uspto-grants-1991_03
Patent number
US05001125

Linked notes

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