Methyl Isobutyl Ketone → N-{2-[4-(5-chloro-2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)-1-piperidinyl]-ethyl}-4-fluoro-2-nitrobenzamide

HRID 437670Notes

Reaction equation

HRID 437670 reaction equation
Br[CH2:2][CH2:3][NH:4][C:5](=[O:16])[C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][C:7]=1[N+:13]([O-:15])=[O:14].[Cl:17][C:18]1[CH:33]=[CH:32][C:21]2[N:22]([CH:26]3[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]3)[C:23](=[O:25])[NH:24][C:20]=2[CH:19]=1.C(=O)([O-])[O-].[Na+].[Na+].CC(C)CC(=O)C>O>[Cl:17][C:18]1[CH:33]=[CH:32][C:21]2[N:22]([CH:26]3[CH2:27][CH2:28][N:29]([CH2:2][CH2:3][NH:4][C:5](=[O:16])[C:6]4[CH:11]=[CH:10][C:9]([F:12])=[CH:8][C:7]=4[N+:13]([O-:15])=[O:14])[CH2:30][CH2:31]3)[C:23](=[O:25])[NH:24][C:20]=2[CH:19]=1

Participants

6

Reactant 4

HCID 7909Methyl Isobutyl KetoneHCID 10340Sodium CarbonateHCID 1046075-Chloro-1,3-dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-oneHCID 21428900N-(2-bromoethyl)-4-fluoro-2-nitrobenzamide

Product 1

HCID 21428824N-{2-[4-(5-chloro-2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)-1-piperidinyl]-ethyl}-4-fluoro-2-nitrobenzamide

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 7.3 parts of N-(2-bromoethyl)-4-fluoro-2-nitrobenzamide, 6.2 parts of 5-chloro-1,3-dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-one, 5.2 parts of sodium carbonate and 80 parts of 4-methyl-2-pentanone is stirred and refluxed overnight. The reaction mixture is cooled, water is added and the layers are separated. The aqueous phase is extracted with 4-methyl-2-pentanone. The combined organic phases are washed with water, 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 oily residue is crystallized from 2-propanone. The product is filtered off and dried, yielding 1 part of N-{2-[4-(5-chloro-2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)-1-piperidinyl]-ethyl}-4-fluoro-2-nitrobenzamide.

Workup

  1. temperaturerefluxed overnight
  2. temperatureThe reaction mixture is cooled
  3. customthe layers are separated
  4. extractionThe aqueous phase is extracted with 4-methyl-2-pentanone
  5. washThe combined organic phases are washed with water
  6. customdried
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue is purified by column-chromatography over silica gel using
  10. additiona mixture of trichloromethane and methanol (90:10 by volume) as eluent
  11. customThe pure fractions are collected
  12. customthe eluent is evaporated
  13. customThe oily residue is crystallized from 2-propanone
  14. filtrationThe product is filtered off
  15. customdried

Sources & evidence

ORD record
ord-cdd75b18697b4468a6236fe5ffc4adc3
Source dataset
uspto-grants-1977_06
Patent number
US04031226

Reaction notes

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