Dimethylformamide → [1-[(4-Fluorophenyl)methyl]-1H-benzimidazol-2-yl][1-[2-(4-methoxyphenyl)ethyl]-4-piperidinyl]methanone

HRID 1647048Notes

Reaction equation

HRID 1647048 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[N:11]=[C:10]2[C:18]([CH:20]2[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)=[O:19])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].CN(C=O)C.Br[CH2:38][CH2:39][C:40]1[CH:45]=[CH:44][C:43]([O:46][CH3:47])=[CH:42][CH:41]=1>C1(C)C=CC=CC=1.C(OCC)(=O)C.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[N:11]=[C:10]2[C:18]([CH:20]2[CH2:25][CH2:24][N:23]([CH2:38][CH2:39][C:40]3[CH:45]=[CH:44][C:43]([O:46][CH3:47])=[CH:42][CH:41]=3)[CH2:22][CH2:21]2)=[O:19])=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 844271-(2-Bromoethyl)-4-methoxybenzeneHCID 155428834-(1-(4-fluorobenzyl)-1H-benzimidazole-2-carbonyl)piperidine

Product 1

HCID 10917690[1-[(4-Fluorophenyl)methyl]-1H-benzimidazol-2-yl][1-[2-(4-methoxyphenyl)ethyl]-4-piperidinyl]methanone

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

To a stirred, room temperature, mixture of [1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]-4-piperidinylmethanone, mono (trifluoroacetate) (1.82 g, 4.03×10-3 mole), potassium carbonate (1.39 g, 1.00×10-2 mole), and sieve dry DMF (15 ml) was added 1-(2-bromoethyl)-4-methoxybenzene (0.87 g, 4.04×10-3 mole). The reaction was then immersed in an oil bath which had been preheated to ca. 90° C. After being stirred at between 80-90° C. for 22 hours, the reaction was allowed to cool to room temperature. The reaction was poured into a separatory funnel containing H2O and a 2:1 mixture of ethyl acetate:toluene. The two phases were mixed and the aqueous layer was separated. The organic layer was washed two times with H2O and once with saturated aqueous NaCl before being dried over anhydrous Na2SO4. The drying agent was removed by filtration and the filtrate was evaporated at reduced pressure leaving an oil which was purified by flash chromatography (ethyl acetate). Crystallization from cyclohexane afforded [1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl][1-[2-(4-methoxyphenyl)ethyl]-4-piperidinyl]methanone as off white matted needles: 1.08 g (57%). This material was spectroscopically identical with the previously described product of Example III.

Workup

  1. customThe reaction was then immersed in an oil bath
  2. customhad been preheated to ca. 90° C
  3. temperatureto cool to room temperature
  4. additionThe reaction was poured into a separatory funnel
  5. additionThe two phases were mixed
  6. customthe aqueous layer was separated
  7. washThe organic layer was washed two times with H2O
  8. dry with materialonce with saturated aqueous NaCl before being dried over anhydrous Na2SO4
  9. customThe drying agent was removed by filtration
  10. customthe filtrate was evaporated at reduced pressure
  11. customleaving an oil which
  12. customwas purified by flash chromatography (ethyl acetate)
  13. customCrystallization from cyclohexane

Sources & evidence

ORD record
ord-934025c553bb4e5b92cda5bca843f8b7
Source dataset
uspto-grants-1993_01
Patent number
US05182399

Reaction notes

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