Benzoic Acid → 4-Amino-3-fluorobenzophenone

HRID 841184Notes

Reaction equation

HRID 841184 reaction equation
[C:1]([OH:9])(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:10][C:11]1[CH:17]=[CH:16][CH:15]=[CH:14][C:12]=1[NH2:13]>>[NH2:13][C:12]1[CH:14]=[CH:15][C:16]([C:1]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[O:9])=[CH:17][C:11]=1[F:10]

Participants

3

Reactant 2

HCID 243Benzoic AcidHCID 95842-Fluoroaniline

Product 1

HCID 107750394-Amino-3-fluorobenzophenoneYield 46.4%

Conditions

Temperature
200 °C

Procedure

To stirred polyphosphoric acid (125 g) at 90° C. was added benzoic acid (18.32 g) and 2-fluoroaniline (8.33 g) and the bath temperature was raised to 200° C. for 1 hour. The heating bath was removed and the stirred mixture was treated cautiously with water (60 ml). The mixture was stirred at 140-160° C. for 1 hour, the heating bath was removed, and 3M hydrochloric acid was added (50 ml). The mixture was poured into water (750 ml) and filtered through diatomaceous earth with a dichloromethane wash. The filtrate was made basic with 15% sodium hydroxide and the mixture was again filtered through diatomaceous earth with a dichloromethane wash. The combined dichloromethane extracts were washed (saturated aqueous sodium hydrogen carbonate), dried, filtered, and evaporated. Chromatography, with ether/hexanes (gradient, 10/90 to 50/50) as the eluent, followed by recrystallization from hexanes, yielded the title compound as a light yellow solid (7.48 g). M.p. 83-85° C.; MS: 216 (M+H); NMR (400 MHz): 6.27 (brs, 2H), 6.80 (t, 1H, J=8.6), 7.36 (q, 1H, J=8.4, 1.9), 7.41 (q, 1H, J=12.4, 1.9), 7.49-7.51 (m, 2H) 7.60-7.63 (m, 3H); EA: C13H10FNO requires C, 72.55; H, 4.68; N, 6.51%; found: C, 72.51; H, 4.82; N, 6.42%.

Workup

  1. customThe heating bath was removed
  2. additionthe stirred mixture was treated cautiously with water (60 ml)
  3. customthe heating bath was removed
  4. addition3M hydrochloric acid was added (50 ml)
  5. additionThe mixture was poured into water (750 ml)
  6. filtrationfiltered through diatomaceous earth with a dichloromethane
  7. washwash
  8. filtrationthe mixture was again filtered through diatomaceous earth with a dichloromethane
  9. washwash
  10. washThe combined dichloromethane extracts were washed (saturated aqueous sodium hydrogen carbonate)
  11. customdried
  12. filtrationfiltered
  13. customevaporated
  14. customChromatography, with ether/hexanes (gradient, 10/90 to 50/50) as the eluent, followed by recrystallization from hexanes

Sources & evidence

ORD record
ord-d0e172eba4ec4fb29c4df8dd77c110fd
Source dataset
uspto-grants-2002_04
Patent number
US06369273B1

Reaction notes

Loading…