Imidazole → 1-(2-Methoxyphenyl)-4-[1-(3,5-dimethylpyridin-2-yl)-cyclohex-1-en-4-yl]piperazine

HRID 54205Notes

Reaction equation

HRID 54205 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][N:12]([CH:15]2[CH2:20][CH2:19][C:18](O)([C:21]3[C:26]([CH3:27])=[CH:25][C:24]([CH3:28])=[CH:23][N:22]=3)[CH2:17][CH2:16]2)[CH2:11][CH2:10]1.N1C=CN=C1>C1COCC1>[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][N:12]([CH:15]2[CH2:20][CH2:19][C:18]([C:21]3[C:26]([CH3:27])=[CH:25][C:24]([CH3:28])=[CH:23][N:22]=3)=[CH:17][CH2:16]2)[CH2:11][CH2:10]1

Participants

4

Reactant 2

HCID 795ImidazoleHCID 199585321-(2-Methoxyphenyl)-4-[1-hydroxy-1(3,5-dimethylpyridin-2-yl)-cyclohex-4-yl]piperazine

Product 1

HCID 199585461-(2-Methoxyphenyl)-4-[1-(3,5-dimethylpyridin-2-yl)-cyclohex-1-en-4-yl]piperazineYield 61.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Methyloxalyl chloride (0.35 ml) was added to a mixture of 1-(2-methoxyphenyl)-4-[1-hydroxy-1(3,5-dimethylpyridin-2-yl)-cyclohex-4-yl]piperazine (0.7 g, 1.8 mmol) and imidazole (0.25 g) in THF (15 ml) at reflux. Heating was continued overnight when the solvent was evaporated in vacuo and replaced with toluene (15 ml). The mixture was heated under reflux overnight, then, when cool, added to dilute NaOH (aq) and extracted by ether (3×50 ml). The combined organic extracts were washed with brine (50 ml) and water (50 ml), dried over magnesium sulphate and evaporated to dryness. The crude product was chromatographed (SiO2, 2% methanol in dichloromethane) giving the title compound (0.42 g) which was recrystallised from hexane then treated with ethanolic HCl to give the title compound as the trihydrochloride 2.25 hydrate, m.p. 235°-236° C.

Workup

  1. temperatureat reflux
  2. temperatureHeating
  3. customwhen the solvent was evaporated in vacuo
  4. temperatureThe mixture was heated
  5. temperatureunder reflux overnight
  6. temperaturewhen cool
  7. additionadded to dilute NaOH (aq)
  8. extractionextracted by ether (3×50 ml)
  9. washThe combined organic extracts were washed with brine (50 ml) and water (50 ml)
  10. dry with materialdried over magnesium sulphate
  11. customevaporated to dryness
  12. customThe crude product was chromatographed (SiO2, 2% methanol in dichloromethane)

Sources & evidence

ORD record
ord-62455fba6cda438398767cd6e97e7565
Source dataset
uspto-grants-1997_04
Patent number
US05622951

Reaction notes

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