Methyl Isobutyl Ketone → 1-{2-[4-(4-fluorobenzoyl)-1-piperidinyl]ethyl}-1,3-dihydro-2H-benzimidazol-2-one

HRID 258851Notes

Reaction equation

HRID 258851 reaction equation
CS(O[CH2:6][CH2:7][N:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[NH:10][C:9]1=[O:17])(=O)=O.Cl.[F:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]([CH:28]2[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)=[O:27])=[CH:22][CH:21]=1.C(=O)([O-])[O-].[Na+].[Na+].CC(C)CC(=O)C>O>[F:19][C:20]1[CH:21]=[CH:22][C:23]([C:26]([CH:28]2[CH2:33][CH2:32][N:31]([CH2:6][CH2:7][N:8]3[C:12]4[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=4[NH:10][C:9]3=[O:17])[CH2:30][CH2:29]2)=[O:27])=[CH:24][CH:25]=1

Participants

6

Reactant 4

HCID 7909Methyl Isobutyl KetoneHCID 10340Sodium CarbonateHCID 3084438p-Fluorophenyl 4-piperidyl ketone hydrochlorideHCID 214248212-(2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)ethyl methanesulfonate

Product 1

HCID 118247341-{2-[4-(4-fluorobenzoyl)-1-piperidinyl]ethyl}-1,3-dihydro-2H-benzimidazol-2-one

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

A mixture of 5.6 parts of 2-(2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)ethyl methanesulfonate, 4.9 parts of (4-fluorophenyl) (4-piperidinyl) methanone hydrochloride, 8 parts of sodium carbonate and 200 parts of 4-methyl-2-pentanone is stirred and refluxed for 7 hours with water-separator. After cooling, water is added and the layers are separated. The organic phase is dried, filtered and evaporated. The oily 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 4-methyl-2-pentanone, yielding 4.3 parts of 1-{2-[4-(4-fluorobenzoyl)-1-piperidinyl]ethyl}-1,3-dihydro-2H-benzimidazol-2-one; mp. 163.6° C.

Workup

  1. temperatureAfter cooling
  2. customthe layers are separated
  3. customThe organic phase is dried
  4. filtrationfiltered
  5. customevaporated
  6. customThe oily residue is purified by column-chromatography over silica gel using
  7. additiona mixture of trichloromethane and 10% of methanol as eluent
  8. customThe pure fractions are collected
  9. customthe eluent is evaporated
  10. customThe residue is crystallized from 4-methyl-2-pentanone

Sources & evidence

ORD record
ord-b522cecae3074ee7958b16dd89730cac
Source dataset
uspto-grants-1977_07
Patent number
US04035369

Reaction notes

Loading…