p-Toluenesulfonic acid → HCID 178437400, compound

HRID 928817Notes

Reaction equation

HRID 928817 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 58: 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 h, 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 min, the mixture was cooled to room temperature. Ether (100 mL) and hexanes (50 mL) were added. The mixture was allowed to stir for 30 min during which time a white solid crashed out of solution. The whole was filtered through paper, rinsing with ether. The gummy solids were collected. Acetonitrile (20 mL) was added and the mixture was sonicated for 5 min. The slurry was filtered through 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 min
  7. temperaturethe mixture was cooled to room temperature
  8. filtrationThe whole was filtered through paper
  9. washrinsing with ether
  10. customThe gummy solids were collected
  11. additionAcetonitrile (20 mL) was added
  12. customthe mixture was sonicated for 5 min
  13. filtrationThe slurry was filtered through paper
  14. washthe solids were rinsed with acetonitrile
  15. customThe off-white solids were collected
  16. customdried
  17. customused in the next step without further purification

Sources & evidence

ORD record
ord-b642eb4bfd5f4bc0abd1285c666ead78
Source dataset
uspto-grants-2016_03
Patent number
US09290476B2

Reaction notes

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