Piperazine → 3-Fluoro-4-piperazin-1-yl-benzonitrile

HRID 875013

Reaction equation

HRID 875013 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1F)[C:5]#[N:6].[NH:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1>CN(C)C(=O)C.O>[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[N:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1)[C:5]#[N:6]

Participants

5

Reactant 2

HCID 4837PiperazineHCID 5872033,4-Difluorobenzonitrile

Product 1

HCID 5961133-Fluoro-4-piperazin-1-yl-benzonitrileYield 95.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
120 °C

Procedure

3,4-Difluorobenzonitrile (2.0 g, 14.3 mmol) and piperazine (6.19 g, 71.8 mmol) were dissolved in N,N-dimethylacetamide (10 mL) and the solution was heated to 120° C. for 1.5 h. The reaction mixture was cooled to room temperature, diluted with water, and extracted with EtOAc. The combined extracts were washed with water and brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure to get 3-fluoro-4-(piperazin-1-yl)benzonitrile (2.8 g, yield 95%), which was carried through without further purification. 1H NMR (400 MHz, DMSO-d6) δ 7.69-7.65 (dd, J=13.6 Hz, 2.0 Hz, 1H), 7.56-7.53 (dd, J=8.5 Hz, 1.8 Hz, 1H), 7.12-7.07 (d, J=8.7 Hz, 1H), 3.08-3.05 (m, 4H), 2.83-2.80 (m, 4H). MS (ESI) m/z: Calculated for C11H12FN3: 205.10. found: 205.9 (M+H)+

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted with EtOAc
  3. washThe combined extracts were washed with water and brine
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ddb9d8bb25a641a8a773d0704335ff56
Source dataset
uspto-grants-2015_03
Patent number
US08981084B2

Linked notes

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