1-Chloro-4-nitrobenzene → 1-(4,6-Dimethyl-pyridin-2-yl)-4-(4-nitro-phenyl)-piperazine

HRID 1910811Notes

Reaction equation

HRID 1910811 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([N:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)[CH:3]=1.Cl[C:16]1[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1>C1(C)C=CC=CC=1.C1COCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([N:9]2[CH2:10][CH2:11][N:12]([C:16]3[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=3)[CH2:13][CH2:14]2)[CH:3]=1

Participants

8

Reactant 4

HCID 74741-Chloro-4-nitrobenzeneHCID 10796Cesium carbonateHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 233680631-(4,6-Dimethylpyridin-2-YL)piperazine

Product 1

HCID 668512921-(4,6-Dimethyl-pyridin-2-yl)-4-(4-nitro-phenyl)-piperazine

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 1-(4,6-dimethyl-pyridin-2-yl)-piperazine (0.7 g, 3.66 mmol) and 1-chloro-4-nitro-benzene (0.69 g, 4.39 mmol) in toluene was added caesium carbonate (2.38 g, 7.32 mmol), then the mixture was stirred for 30 min. under an argon atmosphere. A solution of palladium(II) acetate (50 mg, 0.22 mmol) and (2′-dicyclohexylphosphanyl-biphenyl-2-yl)-dimethyl-amine (50 mg, 0.13 mmol) in THF was purged with argon for 30 min then added to the substrate mixture, and the resulting mixture was heated at 80° C. for 4 h. It was then allowed to cool and concentrated to dryness, and the resulting residue was diluted with water and extracted with ethyl acetate. The combined extracts were washed with brine, dried over sodium sulfate and concentrated in vacuo to a residue which was purified by column chromatography on silica gel (60-120 mesh) using 10% ethyl acetate/petroleum ether as eluent. This afforded 1-(4,6-dimethyl-pyridin-2-yl)-4-(4-nitro-phenyl)-piperazine (0.4 g, 35%).

Workup

  1. additionthen added to the substrate mixture
  2. temperatureto cool
  3. concentrationconcentrated to dryness
  4. additionthe resulting residue was diluted with water
  5. extractionextracted with ethyl acetate
  6. washThe combined extracts were washed with brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated in vacuo to a residue which
  9. customwas purified by column chromatography on silica gel (60-120 mesh)

Sources & evidence

ORD record
ord-69e71089d2654502b4e20e9b8f4b0310
Source dataset
uspto-grants-2013_12
Patent number
US08604029B2

Reaction notes

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