Sodium Carbonate → 5-chloro-1-{3-[4-(4-chlorophenyl)-4-hydroxy-1-piperidinyl]propyl}-1,3-dihydro-2H-benzimidazol-2-one

HRID 46886

Reaction equation

HRID 46886 reaction equation
CS(O)(=O)=O.[Cl:6][C:7]1[CH:20]=[CH:19][C:10]2[N:11]([CH2:15][CH2:16][CH2:17]O)[C:12](=[O:14])[NH:13][C:9]=2[CH:8]=1.[Cl:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2([OH:34])[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)=[CH:24][CH:23]=1.C(=O)([O-])[O-].[Na+].[Na+]>CC(C)CC(=O)C>[Cl:6][C:7]1[CH:20]=[CH:19][C:10]2[N:11]([CH2:15][CH2:16][CH2:17][N:31]3[CH2:30][CH2:29][C:28]([C:25]4[CH:26]=[CH:27][C:22]([Cl:21])=[CH:23][CH:24]=4)([OH:34])[CH2:33][CH2:32]3)[C:12](=[O:14])[NH:13][C:9]=2[CH:8]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 382824-(4-Chlorophenyl)-4-hydroxypiperidineHCID 867353595-chloro-1,3-dihydro-1-(3-hydroxypropyl)-2H-benzimidazol-2-one methanesulfonate

Product 1

HCID 203855705-chloro-1-{3-[4-(4-chlorophenyl)-4-hydroxy-1-piperidinyl]propyl}-1,3-dihydro-2H-benzimidazol-2-oneYield 24%

Reagents, catalysts & solvents 1

HCID 7909Methyl Isobutyl KetoneSolvent

Procedure

A mixture of 6.7 parts of 5-chloro-1,3-dihydro-1-(3-hydroxypropyl)-2H-benzimidazol-2-one methanesulfonate, 4.2 parts of 4-(4-chlorophenyl)-4-piperidinol, 3.2 parts of sodium carbonate and 32 parts of 4-methyl-2-pentanone is stirred and heated at 50°-60° C. for 1.50 hours. The reaction mixture is poured onto ice-water. The precipitated product is filtered off and dissolved in trichloromethane. The solution is washed with water, dried, filtered and evaporated. The solid 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 solid residue is stirred in a small amount of trichloromethane. The product is filtered off and crystallized from 4-methyl-2-pentanone, yielding 2 parts (24%) of 5-chloro-1-{3-[4-(4-chlorophenyl)-4-hydroxy-1-piperidinyl]propyl}-1,3-dihydro-2H-benzimidazol-2-one; mp. 190.8° C.

Workup

  1. temperatureheated at 50°-60° C. for 1.50 hours
  2. additionThe reaction mixture is poured onto ice-water
  3. filtrationThe precipitated product is filtered off
  4. dissolutiondissolved in trichloromethane
  5. washThe solution is washed with water
  6. customdried
  7. filtrationfiltered
  8. customevaporated
  9. customThe solid 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. stirringThe solid residue is stirred in a small amount of trichloromethane
  14. filtrationThe product is filtered off
  15. customcrystallized from 4-methyl-2-pentanone

Sources & evidence

ORD record
ord-49cd37f1118140bb940d3bc8aa2a4093
Source dataset
uspto-grants-1979_11
Patent number
US04175129

Linked notes

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