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

HRID 258855Notes

Reaction equation

HRID 258855 reaction equation
CS(O[CH2:6][CH2:7][CH2:8][N:9]1[C:13]2[C:14]([Cl:18])=[CH:15][CH:16]=[CH:17][C:12]=2[NH:11][C:10]1=[O:19])(=O)=O.Cl.[F:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]([CH:30]2[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]2)=[O:29])=[CH:24][CH:23]=1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O>[Cl:18][C:14]1[C:13]2[N:9]([CH2:8][CH2:7][CH2:6][N:33]3[CH2:34][CH2:35][CH:30]([C:28](=[O:29])[C:25]4[CH:24]=[CH:23][C:22]([F:21])=[CH:27][CH:26]=4)[CH2:31][CH2:32]3)[C:10](=[O:19])[NH:11][C:12]=2[CH:17]=[CH:16][CH:15]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 3084438p-Fluorophenyl 4-piperidyl ketone hydrochlorideHCID 214248143-(7-chloro-2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)propyl methanesulfonate

Product 1

HCID 214248284-chloro-3-{3-[4-(4-fluorobenzoyl)-1-piperidinyl]-propyl}-1,3-dihydro-2H-benzimidazol-2-oneYield 18%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
55 °C

Procedure

A mixture of 4.4 parts of 3-(7-chloro-2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)propyl methanesulfonate, 3.4 parts of (4-fluorophenyl) (4-piperidinyl) methanone hydrochloride, 5 parts of sodium carbonate and 45 parts of N,N-dimethylformamide is stirred for 6 hours at 50-60° C. The reaction mixture is cooled and poured onto water. The product is extracted with 4-methyl-2-pentanone. The extract is 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 part (18%) of 4-chloro-3-{3-[4-(4-fluorobenzoyl)-1-piperidinyl]-propyl}-1,3-dihydro-2H-benzimidazol-2-one; mp. 138° C.

Workup

  1. temperatureThe reaction mixture is cooled
  2. additionpoured onto water
  3. extractionThe product is extracted with 4-methyl-2-pentanone
  4. customThe extract is dried
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue is purified by column-chromatography over silica gel using
  8. additiona mixture of trichloromethane and 10% of methanol as eluent
  9. customThe pure fractions are collected
  10. customthe eluent is evaporated
  11. customThe residue is crystallized from a mixture of 4-methyl-2-pentanone and 2,2'-oxybispropane

Sources & evidence

ORD record
ord-1bb9798839e5417984d91c8b62c36276
Source dataset
uspto-grants-1977_07
Patent number
US04035369

Reaction notes

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