Potassium Iodide → 6-chloro-1-{3-[4-(4-fluorobenzoyl)-1-piperidinyl] propyl}-1,3-dihydro-2H-benzimidazol-2-one

HRID 258854Notes

Reaction equation

HRID 258854 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:9][C:8](=[O:10])[N:7]([CH2:11][CH2:12][CH2:13]Cl)[C:6]=2[CH:15]=1.Cl.[F:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]([CH:26]2[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)=[O:25])=[CH:20][CH:19]=1.C(=O)([O-])[O-].[Na+].[Na+].[I-].[K+]>O.CC(C)CC(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:9][C:8](=[O:10])[N:7]([CH2:11][CH2:12][CH2:13][N:29]3[CH2:30][CH2:31][CH:26]([C:24](=[O:25])[C:21]4[CH:20]=[CH:19][C:18]([F:17])=[CH:23][CH:22]=4)[CH2:27][CH2:28]3)[C:6]=2[CH:15]=1

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 10340Sodium CarbonateHCID 3084438p-Fluorophenyl 4-piperidyl ketone hydrochlorideHCID 203855876-chloro-1-(3-chloropropyl)-1,3-dihydro-2H-benzimidazol-2-one

Product 1

HCID 214248236-chloro-1-{3-[4-(4-fluorobenzoyl)-1-piperidinyl] propyl}-1,3-dihydro-2H-benzimidazol-2-oneYield 23%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 7909Methyl Isobutyl KetoneSolvent

Procedure

A mixture of 5.6 parts of 6-chloro-1-(3-chloropropyl)-1,3-dihydro-2H-benzimidazol-2-one, 4.9 parts of (4-fluorophenyl) (4-piperidinyl) methanone hydrochloride, 8.5 parts of sodium carbonate, 0.2 parts of potassium iodide and 200 parts of 4-methyl-2-pentanone is stirred and refluxed overnight with water-separator. After cooling, water is added and the layers are separated. The 4-methyl-2-pentanone-phase is dried, filtered and evaporated. The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and 5% of methanol as eluent. The pure fractions are collected and the eluent is evaporated. The residue is crystallized from 2-propanol, yielding 1.9 parts (23%) of 6-chloro- 1-{3-[4-(4-fluorobenzoyl)-1-piperidinyl] propyl}-1,3-dihydro-2H-benzimidazol-2-one; mp. 157° C.

Workup

  1. temperatureAfter cooling
  2. customthe layers are separated
  3. dry with materialThe 4-methyl-2-pentanone-phase is dried
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue is purified by column-chromatography over silica gel using
  7. additiona mixture of trichloromethane and 5% of methanol as eluent
  8. customThe pure fractions are collected
  9. customthe eluent is evaporated
  10. customThe residue is crystallized from 2-propanol

Sources & evidence

ORD record
ord-c3d230c344584aacba0c231641c48da9
Source dataset
uspto-grants-1977_07
Patent number
US04035369

Reaction notes

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