p-Toluenesulfonic acid → HCID 178437400, compound

HRID 926451Notes

Reaction equation

HRID 926451 reaction equation
O=[C:2]([CH2:20][CH3:21])[CH:3]([CH2:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=1)[C:4]([O:6]CC)=O.[Br:22][C:23]1[CH:29]=[CH:28][C:26]([NH2:27])=[CH:25][CH:24]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.C1(OC2C=CC=CC=2)C=CC=CC=1>CCOCC.C1(C)C=CC=CC=1>[Br:22][C:23]1[CH:24]=[C:25]2[C:26](=[CH:28][CH:29]=1)[N:27]=[C:2]([CH2:20][CH3:21])[C:3]([CH2:9][C:10]1[CH:11]=[CH:12][C:13]([C:16]([F:17])([F:18])[F:19])=[CH:14][CH:15]=1)=[C:4]2[OH:6]

Participants

7

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 7583Diphenyl EtherHCID 78074-BromoanilineHCID 86715647HCID 86715647, compound

Product 1

HCID 178437400HCID 178437400, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
125 °C

Procedure

A round-bottomed flask equipped with a Dean-Stark apparatus was charged with ethyl 3-oxo-2-(4-(trifluoromethyl)benzyl)pentanoate (8.84 g, 29.2 mmol, Intermediate 5: step a), 4-bromoaniline (5.00 g, 29.2 mmol), para-toluenesulfonic acid (0.503 g, 2.9 mmol), and toluene (146 mL). The mixture was heated to 125° C. After 18 hours, the flask was cooled to room temperature. The toluene was removed by rotary evaporation to provide an amber colored solid. A mixture of the solid and diphenyl ether (29.1 mL) was heated to 220° C. After 70 minutes, the mixture was cooled to room temperature. Ether (100 mL) and hexanes (50 mL) were added. The mixture was allowed to stir for 30 minutes during which time a white solid crashed out of solution. The suspension was filtered through filter paper, rinsing with ether. The gummy solids were collected. Acetonitrile (20 mL) was added and the mixture was sonicated for 5 minutes. The slurry was filtered through filter paper and the solids were rinsed with acetonitrile. The off-white solids were collected, dried, and then used in the next step without further purification.

Workup

  1. customA round-bottomed flask equipped with a Dean-Stark apparatus
  2. temperaturethe flask was cooled to room temperature
  3. customThe toluene was removed by rotary evaporation
  4. customto provide an amber
  5. temperaturewas heated to 220° C
  6. waitAfter 70 minutes
  7. temperaturethe mixture was cooled to room temperature
  8. filtrationThe suspension was filtered
  9. filtrationthrough filter paper
  10. washrinsing with ether
  11. customThe gummy solids were collected
  12. additionAcetonitrile (20 mL) was added
  13. customthe mixture was sonicated for 5 minutes
  14. filtrationThe slurry was filtered
  15. filtrationthrough filter paper
  16. washthe solids were rinsed with acetonitrile
  17. customThe off-white solids were collected
  18. customdried
  19. customused in the next step without further purification

Sources & evidence

ORD record
ord-0453f64354af4def96bc54f9796edc9a
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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