Dimethyl Sulfoxide → 1-Benzyl-4-[4-(3-chloro-4-fluoro-phenyl)-1-ethyl-1H-imidazol-2-yl]-piperidine

HRID 419719Notes

Reaction equation

HRID 419719 reaction equation
CS(C)=O.[OH-].[K+].[CH2:7]([N:14]1[CH2:19][CH2:18][CH:17]([C:20]2[NH:21][C:22]([C:25]3[CH:30]=[CH:29][C:28]([F:31])=[C:27]([Cl:32])[CH:26]=3)=[CH:23][N:24]=2)[CH2:16][CH2:15]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.I[CH2:34][CH3:35]>O.[Cl-].[Na+]>[CH2:7]([N:14]1[CH2:19][CH2:18][CH:17]([C:20]2[N:24]([CH2:34][CH3:35])[CH:23]=[C:22]([C:25]3[CH:30]=[CH:29][C:28]([F:31])=[C:27]([Cl:32])[CH:26]=3)[N:21]=2)[CH2:16][CH2:15]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 6340IodoethaneHCID 14797Potassium HydroxideHCID 666498081-Benzyl-4-[5-(3-chloro-4-fluoro-phenyl)-1H-imidazol-2-yl]-piperidine

Product 1

HCID 666498541-Benzyl-4-[4-(3-chloro-4-fluoro-phenyl)-1-ethyl-1H-imidazol-2-yl]-piperidineYield 81.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 5234Sodium ChlorideSolvent

Procedure

Add dimethyl sulfoxide (0.3 M, 2.7 mL) to powdered potassium hydroxide (1.5 equiv, 1.217 mmoles; 68 mg). Add 1-Benzyl-4-[5-(3-chloro-4-fluoro-phenyl)-1H-imidazol-2-yl]-piperidine (300 mg, 1.00 equiv; 0.811 mmoles), dropwise add iodoethane (1.1 equiv, 0.892 mmoles; 71 μL) over 8 min. Stir the reaction for 60 minutes, then dilute with water (120 mL) plus saturated sodium chloride (25 mL) and extract four times with DCM. Wash the organic extracts with water, then saturated aqueous sodium chloride, and dry with MgSO4. Filter and purify on silica gel with 10% methanol/acetonitrile to give 262 mg (0.659 mmol, 81%) of 1-Benzyl-4-[4-(3-chloro-4-fluoro-phenyl)-1-ethyl-1H-imidazol-2-yl]-piperidine.

Workup

  1. customthe reaction for 60 minutes
  2. extractionextract four times with DCM
  3. washWash the organic extracts with water
  4. dry with materialsaturated aqueous sodium chloride, and dry with MgSO4
  5. filtrationFilter
  6. custompurify on silica gel with 10% methanol/acetonitrile

Sources & evidence

ORD record
ord-8ecc87ed590242d9adb9641ee69dae58
Source dataset
uspto-grants-2012_01
Patent number
US08093383B2

Reaction notes

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