Sulfuric Acid → 1-[4-[(4-Fluorophenyl)methyl]phenyl]piperazine

HRID 2186682Notes

Reaction equation

HRID 2186682 reaction equation
F[C:2]1[CH:16]=[CH:15][C:5]([C:6]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)=O)=[CH:4][CH:3]=1.[NH:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1.C(=O)(O)O.[Na].C([SiH](CC)CC)C.S(=O)(=O)(O)O.[OH-].[Na+]>FC(F)(F)C(O)=O.C(N(CC)CC)C.C(#N)C>[F:14][C:11]1[CH:12]=[CH:13][C:8]([CH2:6][C:5]2[CH:15]=[CH:16][C:2]([N:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)=[CH:3][CH:4]=2)=[CH:9][CH:10]=1

Participants

10

Reactant 6

HCID 1118Sulfuric AcidHCID 4837PiperazineHCID 95824,4'-DifluorobenzophenoneHCID 12052TriethylsilaneHCID 14798Sodium HydroxideHCID 24192197Carbonic acid, sodium salt

Product 1

HCID 15199981-[4-[(4-Fluorophenyl)methyl]phenyl]piperazineYield 58%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 6422Trifluoroacetic acidSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
100 °C

Procedure

To a 10 ml acetonitrile solution of 426 mg of 4,4′-difluorobenzophenone and 841 mg of piperazine, 395 mg of triethylamine was added and stirred at 100° C. for 12 hours. After cooling to room temperature, saturated aqueous sodium hydrogenbicarbonate solution was added, followed by extracting with chloroform. The extract was dried, filtered and concentrated under reduced pressure. The residue obtained was dissolved in 5 ml of trifluoroacetic acid and treated with 520 mg of triethylsilane and 60 mg of concentrated sulfuric acid, and stirred at room temperature for 1 hour. The reaction mixture was adjusted to pH=9 to 11 with 10% aqueous sodium hydroxide solution, followed by extracting with ethyl acetate. The extract was dried, filtered and concentrated under reduced pressure to give a residue, which was purified by silica gel column chromatography (chloroform:methanol:water (2% acetic acid)=65:35:5) to give the above-referenced compound, 1-[4-(4-fluorophenyl)methylphenyl]piperazine in an amount of 305 mg (yield 58%).

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionby extracting with chloroform
  3. customThe extract was dried
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue obtained
  7. stirringstirred at room temperature for 1 hour
  8. extractionby extracting with ethyl acetate
  9. customThe extract was dried
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customto give a residue, which
  13. customwas purified by silica gel column chromatography (chloroform:methanol:water (2% acetic acid)=65:35:5)

Sources & evidence

ORD record
ord-0f64e39567f84530a5d0aa752a07bf59
Source dataset
uspto-grants-2002_06
Patent number
US06407099B1

Reaction notes

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