Sodium Carbonate → Milenperone

HRID 258853Notes

Reaction equation

HRID 258853 reaction equation
CS(O[CH2:6][CH2:7][CH2:8][N:9]1[C:13]2[CH:14]=[CH:15][C:16]([Cl:18])=[CH:17][C:12]=2[NH:11][C:10]1=[O:19])(=O)=O.[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+]>CC(C)CC(=O)C>[Cl:18][C:16]1[CH:15]=[CH:14][C:13]2[N:9]([CH2:8][CH2:7][CH2:6][N:32]3[CH2:33][CH2:34][CH:29]([C:27](=[O:28])[C:24]4[CH:23]=[CH:22][C:21]([F:20])=[CH:26][CH:25]=4)[CH2:30][CH2:31]3)[C:10](=[O:19])[NH:11][C:12]=2[CH:17]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 27244404-(4-Fluorobenzoyl)piperidineHCID 214248165-chloro-1,3-dihydro-2-oxo-2H-benzimidazole-1-propanol methanesulfonate

Product 1

HCID 65489MilenperoneYield 10%

Reagents, catalysts & solvents 1

HCID 7909Methyl Isobutyl KetoneSolvent

Procedure

A mixture of 5.5 parts of 3-(5-chloro-2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)propyl methanesulfonate, 3.6 parts of (4-fluorophenyl) (4-piperidinyl) methanone, 6 parts of sodium carbonate and 80 parts of 4-methyl-2-pentanone is stirred and refluxed overnight. After cooling, the reaction mixtue is filtered and the filtrate is 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 4-methyl-2-pentanone. The product is filtered off and recrystallized from 4-methyl-2-pentanone, yielding 0.6 parts (10%) of 5-chloro-1-{3-[4-(4-fluorobenzoyl)-1-piperidinyl] propyl} -1,3-dihydro-2H-benzimidazol-2-one; mp. 163.7° C.

Workup

  1. temperaturerefluxed overnight
  2. temperatureAfter cooling
  3. filtrationthe reaction mixtue is filtered
  4. customthe filtrate is evaporated
  5. customThe residue is purified by column-chromatography over silica gel using
  6. additiona mixture of trichloromethane and 5% of methanol as eluent
  7. customThe pure fractions are collected
  8. customthe eluent is evaporated
  9. customThe residue is crystallized from 4-methyl-2-pentanone
  10. filtrationThe product is filtered off
  11. customrecrystallized from 4-methyl-2-pentanone

Sources & evidence

ORD record
ord-4cc7d476fa38487f8e40dec50a64eece
Source dataset
uspto-grants-1977_07
Patent number
US04035369

Reaction notes

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