1-(2-Methoxyphenyl)piperazine → 1-(3-Cyanopropyl)-4-(2-methoxyphenyl)-piperazine

HRID 254271Notes

Reaction equation

HRID 254271 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1.C([O-])([O-])=O.[K+].[K+].Br[CH2:22][CH2:23][CH2:24][C:25]#[N:26]>CC#N>[C:25]([CH2:24][CH2:23][CH2:22][N:12]1[CH2:13][CH2:14][N:9]([C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[O:2][CH3:1])[CH2:10][CH2:11]1)#[N:26]

Participants

5

Reactant 3

HCID 13461-(2-Methoxyphenyl)piperazineHCID 11430Potassium CarbonateHCID 214124-Bromobutyronitrile

Product 1

HCID 5860711-(3-Cyanopropyl)-4-(2-methoxyphenyl)-piperazineYield 75%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 2-methoxy-phenylpiperazine (8 g), K2CO3 (2.5 eq) and 4-bromobutyronitrile (1.05 eq) in CH3CN (150 mL) was refluxed for 10 h. After filtration and concentration in vacuo, the residue is taken up in AcOEt (1000 ml), washed with H2O, the organic layer is washed with aqueous HCl (50 mL, 1 M). Then the acid layer is washed with AcOEt (2×20 ml) and neutralized with aqueous NH3 (28% in H2O) until pH 11. Extraction is carried out with AcOEt, the organic layer is dried with Na2SO4 and concentrated in vacuo. The residual solid is crystallized in hexane to give the title compound (6.8 g, 75%, mp 74° C.). 1H NMR (200 MHz, CDCl3) δ 1.80-1.94 (m, 2H), 2.43-2.57 (m, 4H), 2.62-2.67 (m, 4H), 3.09 (m, 4H), 3.87 (s, 3H), 6.85-7.04. 13C NMR (50 MHz, CDCl3) δ 14.9, 22.7, 50.5, 53.2, 55.3, 56.3, 111.1, 118.1, 119.8, 120.9, 122.9, 141.1, 152.2.

Workup

  1. temperaturewas refluxed for 10 h
  2. filtrationAfter filtration and concentration in vacuo
  3. washwashed with H2O
  4. washthe organic layer is washed with aqueous HCl (50 mL, 1 M)
  5. washThen the acid layer is washed with AcOEt (2×20 ml)
  6. extractionExtraction
  7. dry with materialthe organic layer is dried with Na2SO4
  8. concentrationconcentrated in vacuo
  9. customThe residual solid is crystallized in hexane

Sources & evidence

ORD record
ord-6d9d2d9cf75a437bb34c998d4bc29355
Source dataset
uspto-grants-2011_01
Patent number
US07875617B2

Reaction notes

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