Piperazine → HCID 4368145, compound

HRID 1027449Notes

Reaction equation

HRID 1027449 reaction equation
[C:1]1([CH:7]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=2)O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.S(Cl)(Cl)=O.[NH:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1>C(Cl)Cl.CC#N>[C:1]1([CH:7]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=2)[N:23]2[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 3

HCID 4837PiperazineHCID 24386Thionyl ChlorideHCID 27774043-(Trifluoromethyl)benzhydrol

Product 1

HCID 4368145HCID 4368145, compoundYield 85.1%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of phenyl(3-(trifluoromethyl)phenyl)methanol (10.0 g, 39.6 mmol) in CH2Cl2 (20 mL) was added thionyl chloride (5.78 mL, 79.3 mmol) dropwise at rt. After the addition, the reaction was warmed to 40° C. for 18 h. The solvent was evaporated in vacuo and the residue was dried under vacuum pump for 1 h. The residue was dissolved in CH3CN and added to a solution of piperazine (13.7 g, 159 mmol) in CH3CN and heated to 100° C. for 12 h. The solvent was removed in vacuo, the residue dissolved in CH2Cl2 (150 mL) and washed with 1N NaOH (150 mL). The organic layer was dried with K2CO3 or Na2SO4, filtered, and concentrated. The crude product 1-(phenyl(3-(trifluoromethyl)phenyl)-methyl)piperazine (10.8 g, 85.0% yield) an oil was used without further purification or can be purified by ISCO flash chromatography using 0-15% 2N NH3 methanol solution in CH2Cl2. MS (ESI, pos. ion) m/z: 321.1 (M+1).

Workup

  1. additionAfter the addition
  2. customThe solvent was evaporated in vacuo
  3. customthe residue was dried under vacuum pump for 1 h
  4. dissolutionThe residue was dissolved in CH3CN
  5. temperatureheated to 100° C. for 12 h
  6. customThe solvent was removed in vacuo
  7. dissolutionthe residue dissolved in CH2Cl2 (150 mL)
  8. washwashed with 1N NaOH (150 mL)
  9. dry with materialThe organic layer was dried with K2CO3 or Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-fc3077d689bc47d5871564ac568e72ed
Source dataset
uspto-grants-2014_05
Patent number
US08735383B2

Reaction notes

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