Potassium Iodide → 1-[5-{4-[bis(4-fluorophenyl)methyl]-1-piperazinyl}pentyl]-1,3-dihydro-2H-benzimidazol-2-one dihydrochloride

HRID 1413516Notes

Reaction equation

HRID 1413516 reaction equation
[Cl:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][N:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[N:9](C(C)=C)[C:8]1=[O:19].[F:20][C:21]1[CH:26]=[CH:25][C:24]([CH:27]([C:34]2[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=2)[N:28]2[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)=[CH:23][CH:22]=1.C(=O)([O-])[O-].[Na+].[Na+].[I-].[K+]>O.CC(C)CC(=O)C>[ClH:1].[ClH:1].[F:40][C:37]1[CH:36]=[CH:35][C:34]([CH:27]([C:24]2[CH:25]=[CH:26][C:21]([F:20])=[CH:22][CH:23]=2)[N:28]2[CH2:29][CH2:30][N:31]([CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][N:7]3[C:11]4[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=4[NH:9][C:8]3=[O:19])[CH2:32][CH2:33]2)=[CH:39][CH:38]=1

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 10340Sodium CarbonateHCID 1529321-(Bis(4-fluorophenyl)methyl)piperazineHCID 205063661-(5-chloropentyl)-1,3-dihydro-3-(1-methylethenyl)-2H-benzimidazol-2-one

Product 1

HCID 867374911-[5-{4-[bis(4-fluorophenyl)methyl]-1-piperazinyl}pentyl]-1,3-dihydro-2H-benzimidazol-2-one dihydrochloride

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 7909Methyl Isobutyl KetoneSolvent

Procedure

A mixture of 6.95 parts of 1-(5-chloropentyl)-1,3-dihydro-3-(1-methylethenyl)-2H-benzimidazol-2-one, 5.7 parts of 1-[bis(4-fluorophenyl)methyl]piperazine, 5.3 parts of sodium carbonate, 0.1 parts of potassium iodide and 160 parts of 4-methyl-2-pentanone is stirred and refluxed overnight. The reaction mixture is cooled to room temperature, water is added and the layers are separated. The organic phase is dried, filtered and evaporated. The residue is stirred and refluxed for 30 minutes with a solution of 12 parts of a concentrated hydrochloric acid solution in 40 parts of ethanol. The solvent is evaporated and the free base is liberated in the conventional manner with a diluted ammonium hydroxide solution. The product is extracted with trichloromethane. The extract is dried, filtered and evaporated. The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (90:10 by volume) as eluent. The pure fractions are collected and the eluent is evaporated. The residue is converted into the hydrochloride salt in ethanol and 2-propanol. The salt is filtered off and dried, yielding 1-[5-{4-[bis(4-fluorophenyl)-methyl]-1-piperazinyl}pentyl]-1,3-dihydro-2H-benzimidazol-2-one dihydrochloride.hydrate; mp. 203.7° C.

Workup

  1. temperaturerefluxed overnight
  2. customthe layers are separated
  3. customThe organic phase is dried
  4. filtrationfiltered
  5. customevaporated
  6. stirringThe residue is stirred
  7. temperaturerefluxed for 30 minutes with a solution of 12 parts of a concentrated hydrochloric acid solution in 40 parts of ethanol
  8. customThe solvent is evaporated
  9. extractionThe product is extracted with trichloromethane
  10. customThe extract is dried
  11. filtrationfiltered
  12. customevaporated
  13. customThe residue is purified by column-chromatography over silica gel using
  14. additiona mixture of trichloromethane and methanol (90:10 by volume) as eluent
  15. customThe pure fractions are collected
  16. customthe eluent is evaporated
  17. filtrationThe salt is filtered off
  18. customdried

Sources & evidence

ORD record
ord-ea375c2d355042ab92804cceed436f4a
Source dataset
uspto-grants-1981_02
Patent number
US04250176

Reaction notes

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