Bromide ion → 1-(2,4-Difluorophenyl)piperazine

HRID 1831459Notes

Reaction equation

HRID 1831459 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1Br.[Br-].[NH:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1.CC(C)([O-])C.[Na+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1

Participants

8

Reactant 5

HCID 259Bromide ionHCID 4837PiperazineHCID 676741-Bromo-2,4-difluorobenzeneHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxide

Product 1

HCID 27346371-(2,4-Difluorophenyl)piperazine

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

1-(2,4-Difluorophenyl)piperazine is prepared from 2,4-difluorobromobenzene. To the bromide (8.0 g, 41.4 mmol), piperazine (21.4 g, 249 mmol), sodium t-butoxide (5.6 g, 58 mmol) and BINAP (1.55 g, 2.5 mmol) in toluene (20 ml), add Pd2(dba)3 (0.477 g, 0.83 mmol). Heat the mixture at 110° C. under N2 for 20 h. Allow to cool and extract with 1N HCl. Basify the extract with NaOH to pH=10, extract with CH2Cl2, dry and concentrate to obtain the title compound as a brown oil.

Workup

  1. temperatureto cool
  2. extractionextract with 1N HCl
  3. extractionBasify the extract with NaOH to pH=10
  4. extractionextract with CH2Cl2
  5. customdry
  6. concentrationconcentrate

Sources & evidence

ORD record
ord-182d5c45a54243968089a43cdef69516
Source dataset
uspto-grants-2006_06
Patent number
US07067655B2

Reaction notes

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