Toluene → 1-(Pyridin-3-yl)piperazine

HRID 564877

Reaction equation

HRID 564877 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.[NH:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1.CC(C)([O-])C.[Na+].C1(C)C=CC=CC=1>O.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].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N:4]1[CH:5]=[CH:6][CH:7]=[C:2]([N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[CH:3]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 4837PiperazineHCID 122863-BromopyridineHCID 23676156Sodium t-butoxide

Product 1

HCID 4372341-(Pyridin-3-yl)piperazineYield 29%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent

Procedure

A mixture of 1.0 g (6.3 mmol) of 3-bromopyridine, 2.2 g (25 mmol) of piperazine, 16 mg of tris(dibenzylideneacetone)-dipalladium(0), 32 mg of (S)-(−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl, 1.3 g (13.4 mmol) of sodium t-butoxide, and 50 ml of toluene was heated under reflux for 24 hours in a nitrogen atmosphere. The reaction mixture was diluted with water and extracted with chloroform. The combined organic layer was washed with a saturated sodium chloride aqueous solution and dried over anhydrous sodium sulfate. The solvent was evaporated off, and the residue was purified by silica gel column chromatography using a 9:1 mixture of chloroform and methanol as a developing solvent to give 0.27 g (29%) of the title compound.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 24 hours in a nitrogen atmosphere
  3. extractionextracted with chloroform
  4. washThe combined organic layer was washed with a saturated sodium chloride aqueous solution
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe solvent was evaporated off
  7. customthe residue was purified by silica gel column chromatography
  8. additiona 9:1 mixture of chloroform and methanol as a developing solvent

Sources & evidence

ORD record
ord-c4240a151e8047849a417902692f5887
Source dataset
uspto-grants-2001_01
Patent number
US06169086A

Linked notes

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