Piperazine → 2-Fluoro-4-(piperazin-1-YL)benzonitrile

HRID 2354565Notes

Reaction equation

HRID 2354565 reaction equation
[NH:1]1[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.C([O-])([O-])=O.[K+].[K+].[F:13][C:14]1[CH:21]=[C:20](F)[CH:19]=[CH:18][C:15]=1[C:16]#[N:17]>CC#N.CCOC(C)=O>[F:13][C:14]1[CH:21]=[C:20]([N:1]2[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]2)[CH:19]=[CH:18][C:15]=1[C:16]#[N:17]

Participants

6

Reactant 3

HCID 4837PiperazineHCID 11430Potassium CarbonateHCID 775452,4-Difluorobenzonitrile

Product 1

HCID 187600452-Fluoro-4-(piperazin-1-YL)benzonitrile

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

Piperazine (20.0 g, 232.3 mmol) and K2CO3 (16.0 g, 118.5 mmol) are dissolved in CH3CN (85 ml). 2,4-Difluoro-benzonitrile (8.5 g, 61.1 mmol) is added and the mixture is stirred for 2 h at rt, then diluted with AcOEt and washed with water. The organic layer is separated, dried over Na2SO4 and evaporated. Excess piperazine is removed by MPLC (100 g silica gel, eluent CH2Cl2:MeOH 85:15). A second chromatographic purification (300 g silica gel, eluent toluene:EtOH:AcOH 4:4:1) yields the acetate salt of 2-fluoro-4-(piperazin-1-yl)-benzonitrile that is crystallized from AcOEt, filtered off and washed with ether. The free base is isolated by extraction with sat. aq. Na2CO3 solution/AcOEt.

Workup

  1. washwashed with water
  2. customThe organic layer is separated
  3. dry with materialdried over Na2SO4
  4. customevaporated
  5. customExcess piperazine is removed by MPLC (100 g silica gel, eluent CH2Cl2:MeOH 85:15)
  6. customA second chromatographic purification (300 g silica gel, eluent toluene:EtOH:AcOH 4:4:1)

Sources & evidence

ORD record
ord-572eca8e33804dc6baa1dcb7fc7ae72d
Source dataset
uspto-grants-2010_07
Patent number
US07754719B2

Reaction notes

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