Reaction #50539

Reaction equation

1,5-dimethyl-4-formyl-2-(4-trifluoromethylphenyl)imidazole

Sodium hydroxide

Sodium cyanoborohydride

1-(2,3,4-trimethoxyphenylmethyl)piperazine

→

1-(2,3,4-trimethoxyphenyl)methyl-4-[(2-(4-trifluoromethylphenyl)-1,5-dimethylimidazol-4-yl)methyl]piperazine

Yield 46.6%

Solvents

Ethanol

Conditions

Workup

1. 1
   Otherthe solvent removed under reduced pressure
2. 2
   Otherthe residue partitioned between methylene chloride/water
3. 3
   FiltrationThe mixture was filtered
4. 4
   Otherthe organic layer separated
5. 5
   Dryingdried over anhydrous magnesium sulfate
6. 6
   Filtrationfiltered
7. 7
   Otherevaporated
8. 8
   OtherThe residue was flash-chromatographed on silica gel
9. 9
   Washeluting with ethyl acetate/methanol/ammonia (97/3/0.5)

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.

Source