Piperazine → 1-[(4-fluorophenyl)(phenyl)methyl]piperazine

HRID 2202594Notes

Reaction equation

HRID 2202594 reaction equation
S(Cl)(Cl)=O.[F:5][C:6]1[CH:11]=[CH:10][C:9]([CH:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)O)=[CH:8][CH:7]=1.C(=O)([O-])O.[Na+].[NH:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1.[I-].[K+].C(=O)([O-])[O-].[K+].[K+]>O.C(OCC)(=O)C>[F:5][C:6]1[CH:11]=[CH:10][C:9]([CH:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)=[CH:8][CH:7]=1

Participants

9

Reactant 6

HCID 4837PiperazineHCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 24386Thionyl ChlorideHCID 516892Sodium BicarbonateHCID 5707534-Fluorobenzhydrol

Product 1

HCID 27789901-[(4-fluorophenyl)(phenyl)methyl]piperazineYield 72.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

Thionyl chloride was added to (±)-(4-fluorophenyl)phenylmethanol, and the mixture was stirred at a room temperature overnight. After the completion of the reaction was confirmed by HPLC, ethyl acetate was added thereto, and water was added to the mixture. The resulting mixture was neutralized with sodium hydrogen carbonate, and then washed water twice and dried over magnesium sulfate. After the solvent was distilled off, the residue was dissolved in acetonitrile, and piperazine (1.7 g, 20 mmol), potassium iodide (3.3 g, 20 mmol), and potassium carbonate (3.3 g, 24 mmol) were added thereto. The mixture was refluxed overnight. After the completion of the reaction was confirmed by HPLC, the insoluble matter was removed, and the solvent was distilled off. The resulting residue was dissolved in ethyl acetate and washed with water 3 times. The organic layer was dried over magnesium sulfate, and then the solvent was distilled off. Thus the title compound (3.9 g, 72.7%) was obtained as a yellowish white solid.

Workup

  1. additionwas added
  2. dry with materialwashed water twice and dried over magnesium sulfate
  3. distillationAfter the solvent was distilled off
  4. dissolutionthe residue was dissolved in acetonitrile
  5. temperatureThe mixture was refluxed overnight
  6. customthe insoluble matter was removed
  7. distillationthe solvent was distilled off
  8. dissolutionThe resulting residue was dissolved in ethyl acetate
  9. washwashed with water 3 times
  10. dry with materialThe organic layer was dried over magnesium sulfate
  11. distillationthe solvent was distilled off

Sources & evidence

ORD record
ord-6ffe4c7a361d4fac9e59a155dab86c0a
Source dataset
uspto-grants-2016_06
Patent number
US09365553B2

Reaction notes

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