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

HRID 386530Notes

Reaction equation

HRID 386530 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-1cf0c06515a543c1bf6dfa10e18a5389
Source dataset
uspto-grants-2013_02
Patent number
US08372841B2

Reaction notes

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