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

HRID 849493Notes

Reaction equation

HRID 849493 reaction equation
[NH:1]1[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.F[C:8]1[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:9]=1[C:10]#[N:11]>CN(C)C(=O)C>[C:10]([C:9]1[CH:8]=[CH:15][C:14]([F:16])=[CH:13][C:12]=1[N:1]1[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1)#[N:11]

Participants

4

Reactant 2

HCID 4837PiperazineHCID 775452,4-Difluorobenzonitrile

Product 1

HCID 193671084-Fluoro-2-(piperazin-1-yl)benzonitrile

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
122 °C

Procedure

A mixture of piperazine (Aldrich; 3.99 g), 2,4-difluorobenzonitrile, and N,N-dimethylacetamide (20 mL) is stirred for 1.5 h at 122° C. After cooling, the mixture is partitioned between dichloromethane and satd. aq. sodium bicarbonate. The organic layers are dried over magnesium sulfate and concentrated. The residue is chromatographed on silica gel and the appropriate fractions are combined and concentrated to give 1.44 g of 1(2-cyano-5-fluorophenyl)piperazine; 1H NMR (CDCl3) δ 3.01, 3.30, 6.56, 6.63, 7.40.

Workup

  1. temperatureAfter cooling
  2. customthe mixture is partitioned between dichloromethane
  3. dry with materialThe organic layers are dried over magnesium sulfate
  4. concentrationconcentrated
  5. customThe residue is chromatographed on silica gel
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-9ef007546ddc48d2936bb14ca1172ab3
Source dataset
uspto-grants-2000_01
Patent number
US06013654

Reaction notes

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