Piperazine → 1-(3,4-Difluorophenyl)piperazine

HRID 1893737Notes

Reaction equation

HRID 1893737 reaction equation
[F:1][C:2]1[CH:3]=[C:4](Br)[CH:5]=[CH:6][C:7]=1[F:8].[NH:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]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].C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[C:4]([N:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

8

Reactant 4

HCID 4837PiperazineHCID 676754-Bromo-1,2-difluorobenzeneHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxide

Product 1

HCID 27831221-(3,4-Difluorophenyl)piperazine

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

In 100 ml of toluene, 5 g (25.91 mmol) of 3,4-difluorobromobenzene, 13.39 g (155.45 mmol) of piperazine, 3.49 g (36.27 mmol) of sodium tert-butoxide, 0.24 g (0.26 mmol) of tris(dibenzylidene-acetone)dipalladium and 0.48 g (0.78 mmol) of BINAP are stirred under reflux overnight. Ethyl acetate is added, the mixture is then washed with water and the organic phase is extracted with 1N hydrochloric acid. The aqueous phase is then washed with ethyl acetate and subsequently adjusted to pH 8. Using dichloromethane, the product is extracted from the aqueous phase. The extract is then dried over magnesium sulphate, the solvent is removed and the target compound is dried under reduced pressure.

Workup

  1. temperatureunder reflux overnight
  2. washthe mixture is then washed with water
  3. extractionthe organic phase is extracted with 1N hydrochloric acid
  4. washThe aqueous phase is then washed with ethyl acetate
  5. extractionUsing dichloromethane, the product is extracted from the aqueous phase
  6. dry with materialThe extract is then dried over magnesium sulphate
  7. customthe solvent is removed
  8. customthe target compound is dried under reduced pressure

Sources & evidence

ORD record
ord-67263a6b237c4feeac449b11119225c7
Source dataset
uspto-grants-2013_08
Patent number
US08513255B2

Reaction notes

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