p-Toluenesulfonic acid → HCID 23284962, compound

HRID 369183Notes

Reaction equation

HRID 369183 reaction equation
C1(C)C=CC(S(O)(=O)=O)=CC=1.O=[C:13]1[CH2:18][CH2:17][N:16]([C:19](=[O:31])[C:20]2[CH:25]=[CH:24][C:23]([N:26]3[CH:30]=[N:29][CH:28]=[N:27]3)=[CH:22][CH:21]=2)[CH2:15][CH2:14]1.[Cl:32][C:33]1[CH:38]=[CH:37][C:36]([CH2:39][CH2:40][NH2:41])=[CH:35][CH:34]=1>C1(C)C=CC=CC=1>[Cl:32][C:33]1[CH:38]=[CH:37][C:36]([CH2:39][CH2:40][NH:41][CH:13]2[CH2:18][CH2:17][N:16]([C:19](=[O:31])[C:20]3[CH:25]=[CH:24][C:23]([N:26]4[CH:30]=[N:29][CH:28]=[N:27]4)=[CH:22][CH:21]=3)[CH2:15][CH2:14]2)=[CH:35][CH:34]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 674302-(4-Chlorophenyl)ethylamineHCID 23284973HCID 23284973, compound

Product 1

HCID 23284962HCID 23284962, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A catalytic amount of p-toluenesulfonic acid was added to a solution of 0.45 g of 4-oxo-1-[4-(1,2,4-triazol-1-yl)benzoyl]piperidine and 0.39 g of 2-(4-chlorophenyl)ethylamine in 10 ml of toluene. The mixture was refluxed by heating, for 5 hours while removing the generated water using a Dean-Stark trap. The reaction mixture was concentrated under reduced pressure. To the residue was added 10 ml of ethanol. Thereto was added 70 mg of sodium borohydride at room temperature. The mixture was stirred at room temperature overnight. The reaction mixture was made acidic with cocentrated hydrochloric acid and then concentrated under reduced pressure. To the residue was added ice water. The mixture was made basic with an aqueous sodium hydroxide solution and extracted with two 30-ml portions of ethyl acetate. The extract was washed with water and a saturated aqueous sodium chloride solution in this order, dried with sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography (eluant: methylene chloride/methanol=25/1) and then recrystallized from ethyl acetate to obtain 4-[2-(4-chlorophenyl)ethylamino]-1-[4-(1,2,4-triazol-1-yl)benzoyl]piperidine as a white powder.

Workup

  1. temperatureThe mixture was refluxed
  2. temperatureby heating, for 5 hours
  3. customwhile removing the generated water using a Dean-Stark trap
  4. concentrationThe reaction mixture was concentrated under reduced pressure
  5. additionTo the residue was added 10 ml of ethanol
  6. additionThereto was added 70 mg of sodium borohydride at room temperature
  7. concentrationconcentrated under reduced pressure
  8. additionTo the residue was added ice water
  9. extractionextracted with two 30-ml portions of ethyl acetate
  10. washThe extract was washed with water
  11. dry with materiala saturated aqueous sodium chloride solution in this order, dried with sodium sulfate
  12. concentrationconcentrated under reduced pressure
  13. customto remove the solvent
  14. customThe residue was purified by silica gel column chromatography (eluant: methylene chloride/methanol=25/1)
  15. customrecrystallized from ethyl acetate

Sources & evidence

ORD record
ord-159f345d2762415dac996e28a759ffb3
Source dataset
uspto-grants-2000_10
Patent number
US06136826

Reaction notes

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