Potassium Carbonate → 4-[4-(2-Fluorophenyl)piperazin-1-yl]butanenitrile

HRID 254273Notes

Reaction equation

HRID 254273 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1.C([O-])([O-])=O.[K+].[K+].Br[CH2:21][CH2:22][CH2:23][C:24]#[N:25]>C(#N)C>[C:24]([CH2:23][CH2:22][CH2:21][N:11]1[CH2:12][CH2:13][N:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[F:1])[CH2:9][CH2:10]1)#[N:25]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 214124-BromobutyronitrileHCID 705291-(2-Fluorophenyl)piperazine

Product 1

HCID 231207404-[4-(2-Fluorophenyl)piperazin-1-yl]butanenitrileYield 98%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

2-Fluorophenyl piperazine (6.5 g) are suspended in acetonitrile (50 ml), anhydrous K2CO3 (1.5 eq) and 4-bromobutyronitrile (1.05 eq) in acetonitrile (25 mL) are added dropwise. The mixture is heated at reflux for 10 h and then filtered, the filtrate is concentrated in vacuo. The residue is taken up in AcOEt and washed three times with water. The organic layer is extracted with hydrochloric acid (1M) and the aqueous acid layer is washed with AcOEt and neutralized with aqueous ammonia (28% in H2O) to pH 11. The extraction is carried out with AcOEt and the organic layer is washed twice with water and dried over Na2SO4. The mixture is concentrated to give the title compound (8.35 g, 98%). 1H NMR (200 MHz, CDCl3) δ 1.80-1.90 (m, 2 H), 2.42-2.49 (m, 2H), 2.52-2.56 (m, 2H), 2.59-2.64 (m, 4H), 3.07-3.13 (m, 4H), 6.91-7.07 (m, 4H). RMN 13C (50 MHz, CDCl3): δ 14.8, 22.6, 50.4, 53.0, 56.2 115.8, 116.2 118.8, 119.7, 122.3, 122.5, 124.3, 124.4, 153.1, 158.0.

Workup

  1. temperatureThe mixture is heated
  2. temperatureat reflux for 10 h
  3. filtrationfiltered
  4. concentrationthe filtrate is concentrated in vacuo
  5. washwashed three times with water
  6. extractionThe organic layer is extracted with hydrochloric acid (1M)
  7. washthe aqueous acid layer is washed with AcOEt and neutralized with aqueous ammonia (28% in H2O) to pH 11
  8. extractionThe extraction
  9. washthe organic layer is washed twice with water
  10. dry with materialdried over Na2SO4
  11. concentrationThe mixture is concentrated

Sources & evidence

ORD record
ord-d9d1ed97382d48ee88579a9701be3a7b
Source dataset
uspto-grants-2011_01
Patent number
US07875617B2

Reaction notes

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