Piperazine → 1-(2-Chloro-4-fluorophenyl)piperazine

HRID 1961688Notes

Reaction equation

HRID 1961688 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[Cl:9].[NH:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1.CC(C)([O-])C.[Na+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=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]>[Cl:9][C:3]1[CH:4]=[C:5]([F:8])[CH:6]=[CH:7][C:2]=1[N:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1

Participants

7

Reactant 4

HCID 4837PiperazineHCID 634876Binap, (A+-)-HCID 27334061-Bromo-2-chloro-4-fluorobenzeneHCID 23676156Sodium t-butoxide

Product 1

HCID 184231511-(2-Chloro-4-fluorophenyl)piperazine

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

A suspension of 1-bromo-2-chloro-4-fluorobenzene (4.19 g, 20 mmoles), piperazine (10.32 g, 120 mmoles), sodium tert-butoxide (2.3 g, 1.5 mmoles), tris(dibenzylideneacetone)dipalladium (366 mg, 0.4 mmoles) and racemic (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (747 mg, 1.2 mmoles) in toluene (2 mL) was heated to 120° C. overnight. The mixture was cooled, filtered and the filtrate concentrated under reduced pressure. The crude residue was purified by column chromatography (silica gel, 0-5% 2N methanolic ammonia in DCM) to provide the title compound.

Workup

  1. temperatureThe mixture was cooled
  2. filtrationfiltered
  3. concentrationthe filtrate concentrated under reduced pressure
  4. customThe crude residue was purified by column chromatography (silica gel, 0-5% 2N methanolic ammonia in DCM)

Sources & evidence

ORD record
ord-7f1f298730794705b9f359e2797fc3d4
Source dataset
uspto-grants-2013_04
Patent number
US08415354B2

Reaction notes

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