Tetrahydrofuran → 1-(2,3-Difluoro-6-nitrophenyl)propan-2-one

HRID 1609073Notes

Reaction equation

HRID 1609073 reaction equation
[H-].[Na+].O1CCCC1.C(OCC)(=O)[CH2:9][C:10]([CH3:12])=[O:11].F[C:18]1[C:23]([F:24])=[C:22]([F:25])[CH:21]=[CH:20][C:19]=1[N+:26]([O-:28])=[O:27]>C(O)(=O)C>[F:24][C:23]1[C:18]([CH2:9][C:10](=[O:11])[CH3:12])=[C:19]([N+:26]([O-:28])=[O:27])[CH:20]=[CH:21][C:22]=1[F:25]

Participants

6

Reactant 4

HCID 8028Tetrahydrofuran3×HCID 8868Ethyl AcetoacetateHCID 24758Sodium hydrideHCID 698711,2,3-Trifluoro-4-nitrobenzene

Product 1

HCID 142688761-(2,3-Difluoro-6-nitrophenyl)propan-2-oneYield 90%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

12.1 g (303 mmol) of 60% sodium hydride was added to 45 ml of tetrahydrofuran, and while cooling with a freezing mixture, 90 ml of tetrahydrofuran containing 39.0 g (300 mmol) of ethyl acetoacetate was dropped to the solution below 20° C. through 30 minutes. After the solution was stirred for 1 hour as was, 90 ml of tetrahydrofuran solution containing 26.6 g (150 mmol) of 2,3,4-trifluoronitrobenzene was dropped to the solution below 10° C. through 30 minutes, and the solution was stirred overnight at room temperature. 27 ml of acetic acid was added to the solution, and the solvent was removed by distillation. The solution was extracted with 500 ml of chloroform, and after drying over magnesium sulfate, the solvent was removed by distillation. 30 ml of 4N hydrochloric acid and 25 ml of acetic acid were added to the solution, and the solution was heated at reflux for 24 hours. 550 ml of concentrated hydrochloric acid and 550 ml of acetic acid were added to the solution, and the solution was heated at reflux for 16 hours. After air-cooling, the solution was extracted with 1 l of chloroform and was washed with 500 ml of water two times. The solution was further washed with 300 ml of aqueous saturated sodium hydrogen carbonate solution two times, and after drying over magnesium sulfate, the solvent was removed by distillation. The residue was separated by the column chromatography (silica gel 300 g, eluent solvent; chloroform: n-hexane=1:3) to obtain 31.2 g of the subject compound (148) in a 90% yield.

Workup

  1. additionwas dropped to the solution below 20° C. through 30 minutes
  2. additionwas dropped to the solution below 10° C. through 30 minutes
  3. stirringthe solution was stirred overnight at room temperature
  4. customthe solvent was removed by distillation
  5. extractionThe solution was extracted with 500 ml of chloroform
  6. dry with materialafter drying over magnesium sulfate
  7. customthe solvent was removed by distillation
  8. addition30 ml of 4N hydrochloric acid and 25 ml of acetic acid were added to the solution
  9. temperaturethe solution was heated
  10. temperatureat reflux for 24 hours
  11. addition550 ml of concentrated hydrochloric acid and 550 ml of acetic acid were added to the solution
  12. temperaturethe solution was heated
  13. temperatureat reflux for 16 hours
  14. temperatureAfter air-cooling
  15. extractionthe solution was extracted with 1 l of chloroform
  16. washwas washed with 500 ml of water two times
  17. washThe solution was further washed with 300 ml of aqueous saturated sodium hydrogen carbonate solution two times
  18. dry with materialafter drying over magnesium sulfate
  19. customthe solvent was removed by distillation
  20. customThe residue was separated by the column chromatography (silica gel 300 g, eluent solvent; chloroform: n-hexane=1:3)

Sources & evidence

ORD record
ord-6d38959dff0c4fc99b9ffd3973f86569
Source dataset
uspto-grants-1995_03
Patent number
US05399553

Reaction notes

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