Potassium Carbonate → 1-[(6-Chloropyridin-3-yl)methyl]-4-methylpiperazine

HRID 748504Notes

Reaction equation

HRID 748504 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8]Cl)=[CH:4][N:3]=1.[CH3:10][N:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[Cl:1][C:2]1[N:3]=[CH:4][C:5]([CH2:8][N:14]2[CH2:15][CH2:16][N:11]([CH3:10])[CH2:12][CH2:13]2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 531671-MethylpiperazineHCID 1554792-Chloro-5-(chloromethyl)pyridine

Product 1

HCID 14735211-[(6-Chloropyridin-3-yl)methyl]-4-methylpiperazineYield 74%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

To a suspension of 2-chloro-5-(chloromethyl)pyridine (971 mg, 5.99 mmol) in acetonitrile (50 mL) was added a solution of N-methylpiperazine (1.20 g, 12.0 mmol) in acetonitrile (3 mL) followed by potassium carbonate (0.83 g, 5.99 mmol). The obtained yellow solution was heated at reflux for 40 min. The mixture was allowed to cool for 10 min and the solvent was removed in vacuo. The residue was partitioned between water, NaCl (s), and ethyl acetate. The aqueous layer was extracted with another portion of ethyl acetate. The combined organic layers were dried (Na2SO4) and the solvent was removed in vacuo affording 1.0 g (74% yield) of the title compound as a yellow oil: 1H NMR (CDCl3, 400 MHz) δ 8.31 (d, J=2 Hz, 1 H), 7.65 (dd, J=8, 2 Hz, 1 H), 7.29 (d, J=8 Hz, 1 H), 3.49 (s, 2 H), 2.46 (br s, 8 H), 2.28 (s, 3 H); 13C NMR (CDCl3, 100 MHz) δ 150.2, 150.1, 139.5, 132.8, 124.0, 59.2, 55.0, 53.0,46.0; MS (ESP) m/z 226 (M++1).

Workup

  1. temperatureThe obtained yellow solution was heated
  2. temperatureat reflux for 40 min
  3. temperatureto cool for 10 min
  4. customthe solvent was removed in vacuo
  5. customThe residue was partitioned between water, NaCl (s), and ethyl acetate
  6. extractionThe aqueous layer was extracted with another portion of ethyl acetate
  7. dry with materialThe combined organic layers were dried (Na2SO4)
  8. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-87030bc5aec94848ab756c26f0be1bd0
Source dataset
uspto-grants-2008_07
Patent number
US07399780B2

Reaction notes

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