Potassium Iodide → 1-{3-[4-(4-fluorobenzoyl)-1-piperidinyl]propyl}-1,3-dihydro-5-(trifluoromethyl)-2H-benzimidazol-2-one

HRID 258858Notes

Reaction equation

HRID 258858 reaction equation
Cl[CH2:2][CH2:3][CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][C:12]([C:14]([F:17])([F:16])[F:15])=[CH:13][C:8]=2[NH:7][C:6]1=[O:18].Cl.[F:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]([CH:29]2[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)=[O:28])=[CH:23][CH:22]=1.C(=O)([O-])[O-].[Na+].[Na+].[I-].[K+]>CC(C)CC(=O)C>[F:20][C:21]1[CH:22]=[CH:23][C:24]([C:27]([CH:29]2[CH2:34][CH2:33][N:32]([CH2:2][CH2:3][CH2:4][N:5]3[C:9]4[CH:10]=[CH:11][C:12]([C:14]([F:17])([F:16])[F:15])=[CH:13][C:8]=4[NH:7][C:6]3=[O:18])[CH2:31][CH2:30]2)=[O:28])=[CH:25][CH:26]=1

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 10340Sodium CarbonateHCID 3084438p-Fluorophenyl 4-piperidyl ketone hydrochlorideHCID 203855741-(3-chloropropyl)-1,3-dihydro-5-(trifluoromethyl)-2H-benzimidazol-2-one

Product 1

HCID 214248291-{3-[4-(4-fluorobenzoyl)-1-piperidinyl]propyl}-1,3-dihydro-5-(trifluoromethyl)-2H-benzimidazol-2-oneYield 20%

Reagents, catalysts & solvents 1

HCID 7909Methyl Isobutyl KetoneSolvent

Procedure

A mixture of 4.2 parts of 1-(3-chloropropyl)-1,3-dihydro-5-(trifluoromethyl)-2H-benzimidazol-2-one, 3.6 parts of (4-fluorophenyl) (4-piperidinyl) methanone hydrochloride, 10 parts of sodium carbonate, 0.1 parts of potassium iodide and 80 parts of 4-methyl-2-pentanone is stirred and heated till reflux. Refluxing is continued overnight. After cooling to room temperature, the reaction mixture is poured onto water. The organic phase is separated, dried, filtered and evaporated. The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and 10% of methanol as eluent. The pure fractions are collected and the eluent is evaporated. The residue is crystallized from a mixture of 4-methyl-2-pentanone and 2,2-oxybispropane, yielding 1.4 -parts (20%) of 1-{3-[4-(4-fluorobenzoyl)-1-piperidinyl]propyl}-1,3-dihydro-5-(trifluoromethyl)-2H-benzimidazol-2-one; mp. 160.2° C.

Workup

  1. temperatureheated
  2. temperaturetill reflux
  3. temperatureRefluxing
  4. additionthe reaction mixture is poured onto water
  5. customThe organic phase is separated
  6. customdried
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue is purified by column-chromatography over silica gel using
  10. additiona mixture of trichloromethane and 10% of methanol as eluent
  11. customThe pure fractions are collected
  12. customthe eluent is evaporated
  13. customThe residue is crystallized from a mixture of 4-methyl-2-pentanone and 2,2-oxybispropane

Sources & evidence

ORD record
ord-f5650945039c4f78b26c4d87d630dc57
Source dataset
uspto-grants-1977_07
Patent number
US04035369

Reaction notes

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