Ethanol → 2-Fluoro-4'-aminobenzophenone

HRID 2292937Notes

Reaction equation

HRID 2292937 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.[NH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(O)C>O>[NH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:4]([C:3]2[CH:7]=[CH:8][CH:9]=[CH:10][C:2]=2[F:1])=[O:6])=[CH:14][CH:13]=1

Participants

5

Reactant 3

HCID 702EthanolHCID 6115AnilineHCID 99352-Fluorobenzoic acid

Product 1

HCID 105128532-Fluoro-4'-aminobenzophenone

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To stirred 90° C. polyphosphoric acid (200 g) was added 14.29 g (10.2 mmol) of 2-fluorobenzoic acid and aniline (9.32 g 10.0 mmol) and the bath temperature raised to 180°-190° C. and held there for 1 hour. A solution was obtained at about 140° C. The heating bath was removed and the stirred mixture (sublimate above the solution) was treated cautiously with 80 mL of water. The mixture was stirred at 140°-155° C. for 1 hour, the heating bath removed, 66 mL of 3N HCl added, the mixture poured into 1 L of water and filtered through a pad of Celite. The filtrate was basified with 15% sodium hydroxide and the solid which formed on stirring was collected. The Celite pad was washed well with methylene chloride, the methylene chloride removed and the residue was combined with the solid obtained from basification of the aqueous phase. The combined material was dissolved in refluxing ethanol (175 mL), and treated hot with 125 mL of water. The brown solid obtaing on cooling was additionally recrystallized twice from ethyl acetate-hexane. Final purification by flash column chromatography (methylene chloride) yielded the aniline as a white solid (5.45 g. 25%); mp 128°-130° C. 1H-NMR (250 MHz, d6-DMSO): 6.32 (s, 2H, NH2) 6.60 (dd, 2H, J=8.6, 1.5 Hz, aromatic) 7.28-7.35 (m, 2H, aromatic) 7.40-7.60 (m, 4H, aromatic). MS (CI, CH4): 216 (M+1).

Workup

  1. temperaturethe bath temperature raised to 180°-190° C.
  2. customA solution was obtained at about 140° C
  3. customThe heating bath was removed
  4. additionthe stirred mixture (sublimate above the solution) was treated cautiously with 80 mL of water
  5. customthe heating bath removed
  6. addition66 mL of 3N HCl added
  7. additionthe mixture poured into 1 L of water
  8. filtrationfiltered through a pad of Celite
  9. customthe solid which formed
  10. stirringon stirring
  11. customwas collected
  12. washThe Celite pad was washed well with methylene chloride
  13. customthe methylene chloride removed
  14. customobtained from basification of the aqueous phase
  15. dissolutionThe combined material was dissolved
  16. temperatureThe brown solid obtaing on cooling
  17. customwas additionally recrystallized twice from ethyl acetate-hexane
  18. customFinal purification by flash column chromatography (methylene chloride)

Sources & evidence

ORD record
ord-533d4f0608af4c418d430fef0cb1eabd
Source dataset
uspto-grants-1997_11
Patent number
US05684198

Reaction notes

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