Sodium Hydroxide → 1-(2,3,4-Trimethoxyphenyl)methyl-4-[(2-(4-trifluoromethylphenyl)-1,5-dimethylimidazol-4-yl)methyl]piperazine

HRID 22261

Reaction equation

HRID 22261 reaction equation
[CH3:1][N:2]1[C:6]([CH3:7])=[C:5]([CH:8]=O)[N:4]=[C:3]1[C:10]1[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=1.[CH3:20][O:21][C:22]1[C:27]([O:28][CH3:29])=[C:26]([O:30][CH3:31])[CH:25]=[CH:24][C:23]=1[CH2:32][N:33]1[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1.C([BH3-])#N.[Na+].[OH-].[Na+]>CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].C(O)C>[CH3:20][O:21][C:22]1[C:27]([O:28][CH3:29])=[C:26]([O:30][CH3:31])[CH:25]=[CH:24][C:23]=1[CH2:32][N:33]1[CH2:34][CH2:35][N:36]([CH2:8][C:5]2[N:4]=[C:3]([C:10]3[CH:15]=[CH:14][C:13]([C:16]([F:17])([F:18])[F:19])=[CH:12][CH:11]=3)[N:2]([CH3:1])[C:6]=2[CH3:7])[CH2:37][CH2:38]1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 21109TrimetazidineHCID 5003444Sodium cyanoborohydrideHCID 152882331,5-Dimethyl-4-formyl-2-(4-trifluoromethylphenyl)imidazole

Product 1

HCID 152882341-(2,3,4-Trimethoxyphenyl)methyl-4-[(2-(4-trifluoromethylphenyl)-1,5-dimethylimidazol-4-yl)methyl]piperazineYield 46.6%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 702EthanolSolvent

Procedure

A solution of 1,5-dimethyl-4-formyl-2-(4-trifluoromethylphenyl)imidazole (0.5 g), 1-(2,3,4-trimethoxyphenylmethyl)piperazine (0.54 g), and titanium(IV)isopropoxide (0.73 g) was allowed to stand for 1 hour at room temperature. Ethanol (10 ml) was added, and the resultant solution was stirred for 1 hour. Sodium cyanoborohydride (90 mg) was then added, and the mixture stirred overnight. Sodium hydroxide was then added until the pH was just over 7, the solvent removed under reduced pressure, and the residue partitioned between methylene chloride/water. The mixture was filtered, the organic layer separated, dried over anhydrous magnesium sulfate, filtered and evaporated. The residue was flash-chromatographed on silica gel, eluting with ethyl acetate/methanol/ammonia (97/3/0.5), to yield 0.45 g of 1-(2,3,4-trimethoxyphenyl)methyl-4-[(2-(4-trifluoromethylphenyl)-1,5-dimethylimidazol-4-yl)methyl]piperazine. Treatment with anhydrous hydrochloric acid in ethanol converted the base to its dihydrochloride salt, m.p. 235° C.

Workup

  1. customthe solvent removed under reduced pressure
  2. customthe residue partitioned between methylene chloride/water
  3. filtrationThe mixture was filtered
  4. customthe organic layer separated
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was flash-chromatographed on silica gel
  9. washeluting with ethyl acetate/methanol/ammonia (97/3/0.5)

Sources & evidence

ORD record
ord-b1edf5cbf45746debeb10b6d854d0415
Source dataset
uspto-grants-1995_06
Patent number
US05428037

Linked notes

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