Water → 4-(1-((1-Benzylpiperidin-2-yl)methyl)-4-(4-fluoro-3-trifluoromethyl-phenyl)-1H-imidazol-2-yl)piperidine-1-carboxylic acid tert-butyl ester

HRID 1685154Notes

Reaction equation

HRID 1685154 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[NH:15][CH:16]=[C:17]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[C:21]([C:26]([F:29])([F:28])[F:27])[CH:20]=3)[N:18]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[K+].Cl.[CH2:33]([N:40]1[CH2:45][CH2:44][CH2:43][CH2:42][C@@H:41]1[CH2:46]Br)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.O>CS(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[N:15]([CH2:46][CH:41]3[CH2:42][CH2:43][CH2:44][CH2:45][N:40]3[CH2:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[CH:16]=[C:17]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[C:21]([C:26]([F:27])([F:28])[F:29])[CH:20]=3)[N:18]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 962WaterHCID 14797Potassium HydroxideHCID 67264853(R)-1-benzyl-2-(bromomethyl)piperidine hydrochlorideHCID 178451792HCID 178451792, compound

Product 1

HCID 593224464-(1-((1-Benzylpiperidin-2-yl)methyl)-4-(4-fluoro-3-trifluoromethyl-phenyl)-1H-imidazol-2-yl)piperidine-1-carboxylic acid tert-butyl esterYield 46%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of 4-[4-(4-fluoro-3-trifluoromethyl-phenyl)-1H-imidazol-2-yl]-piperidine-1-carboxylic acid tert-butyl ester (4.5 g, 0.011 mol, 1.0 eq) in DMSO (100 mL) and add powdered KOH (3.0 g, 0.055 mol, 5.0 eq) at RT under nitrogen atmosphere and stir for 30 minutes. To the resulting solution add (R)-1-benzyl-2-(bromomethyl)piperidine hydrochloride (5.0 g, 0.0165 mol, 1.5 eq) and stir the reaction mass at RT for 16 h. After completion, dilute the reaction with water (100 mL) and extract the compound in EA (3×100 mL). Wash the organic layer with brine (2×50 mL) and dry over anhydrous sodium sulfate. Concentrate the organic layer under reduced pressure and purify on silica (100-200 mesh) using 2% acetone-DCM to get 3.0 g (46%) of the title compound. (ES+): m/z=601 (M+H).

Workup

  1. stirringstir the reaction mass at RT for 16 h
  2. additionAfter completion, dilute
  3. extractionextract the compound in EA (3×100 mL)
  4. washWash the organic layer with brine (2×50 mL)
  5. dry with materialdry over anhydrous sodium sulfate
  6. concentrationConcentrate the organic layer under reduced pressure
  7. custompurify on silica (100-200 mesh)

Sources & evidence

ORD record
ord-c1892684fb6f47aa9b7dacd4cba454a6
Source dataset
uspto-grants-2012_04
Patent number
US08148387B2

Reaction notes

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