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

HRID 54204Notes

Reaction equation

HRID 54204 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:22]([CH3:28])=[N:23][CH:24]=[CH:25][C:26]=3[CH3:27])[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:22]([CH3:28])=[N:23][CH:24]=[CH:25][C:26]=3[CH3:27])=[CH:17][CH2:16]2)[CH2:11][CH2:10]1

Participants

4

Reactant 2

HCID 795ImidazoleHCID 199585441-(2-Methoxyphenyl)-4-[1-hydroxy-1-(2,4-dimethylpyridin-3-yl)-cyclohex-4-yl]piperazine

Product 1

HCID 199585431-(2-Methoxyphenyl)-4-[1-(2,4-dimethylpyridin-3-yl)-cyclohex-1-en-4-yl]piperazineYield 74.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-(2-methoxyphenyl)-4-[1-hydroxy-1-(2,4-dimethylpyridin-3-yl)-cyclohex-4-yl]piperazine (0.8 g, 2.0 mmol) in dry THF (70 ml) under argon was added imidazole (0.3 g, 4.4 mmol) followed by methyl oxalyl chloride (0.6 ml, 6.5 mmol). The non-homogeneous reaction mixture was refluxed for 24 hours. The reaction solvent was removed and replaced with anhydrous toluene (50 ml). The reaction mixture was refluxed for a further 48 hours. The solvent was removed and the residue partioned between water and chloroform. The organic layer was removed and washed with saturated NaCI solution. The resulting organic phase was dried (MgSO4) filtered and reduced to an oil. Purification of the oil by silica gel column chromatography eluting with chloroform/methanol (20/1) gave the title product (560 mg) which was dissolved in chloroform to which ethereal HCl was added. The solvent was removed and the residue recrystallised from methanol/ether to give the title compound as the trihydrochloride, 1.75 hydrate, m.p. 215°-216° C.

Workup

  1. temperatureThe non-homogeneous reaction mixture was refluxed for 24 hours
  2. customThe reaction solvent was removed
  3. temperatureThe reaction mixture was refluxed for a further 48 hours
  4. customThe solvent was removed
  5. customThe organic layer was removed
  6. washwashed with saturated NaCI solution
  7. dry with materialThe resulting organic phase was dried (MgSO4)
  8. filtrationfiltered
  9. customPurification of the oil by silica gel column chromatography
  10. washeluting with chloroform/methanol (20/1)

Sources & evidence

ORD record
ord-c1dbe91f0dc74401b505d42fb95ae9dc
Source dataset
uspto-grants-1997_04
Patent number
US05622951

Reaction notes

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