Dimethyl Sulfoxide → 4-[1-[2-(Benzyl-methyl-amino)-ethyl]-4-(3-chloro-4-fluoro-phenyl)-1H-imidazol-2-yl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1685153Notes

Reaction equation

HRID 1685153 reaction equation
[OH-].[K+].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH:13]([C:16]2[NH:17][CH:18]=[C:19]([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[C:23]([Cl:28])[CH:22]=3)[N:20]=2)[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].CS(C)=O.Cl.[CH2:34]([N:41]([CH2:43][CH2:44]Cl)[CH3:42])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>C(Cl)Cl.O.[Cl-].[Na+].O>[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH:13]([C:16]2[N:17]([CH2:44][CH2:43][N:41]([CH2:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[CH3:42])[CH:18]=[C:19]([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[C:23]([Cl:28])[CH:22]=3)[N:20]=2)[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 14797Potassium HydroxideHCID 12822620N-(2-Chloroethyl)-N-methylbenzylamine hydrochlorideHCID 178451793HCID 178451793, compound

Product 1

HCID 672648564-[1-[2-(Benzyl-methyl-amino)-ethyl]-4-(3-chloro-4-fluoro-phenyl)-1H-imidazol-2-yl]-piperidine-1-carboxylic acid tert-butyl esterYield 79%

Reagents, catalysts & solvents 2

HCID 21908982Water methylene chlorideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

Add powdered KOH (283 mg; 5.05 mmol) and 4-[4-(3-chloro-4-fluoro-phenyl)-1H-imidazol-2-yl]-piperidine-1-carboxylic acid tert-butyl ester (2.02 mmol; 768 mg) to DMSO (6 mL). Then add benzyl-(2-chloro-ethyl)-methylamine hydrochloride (2.22 mmol; 0.49 mL) in one portion and heat to 40° C. for 18 h. Cool, dilute with DCM/water, add brine and separate layers. Wash the organic phase with water, brine, dry over MgSO4, filter and evaporate. Purify on 120 g silica gel with 1% MeOH/DCM to provide the title compound (840.5 mg; 79%). MS (ES): m/z=527 (M+H).

Workup

  1. temperatureCool
  2. customseparate layers
  3. washWash the organic phase with water, brine
  4. dry with materialdry over MgSO4
  5. filtrationfilter
  6. customevaporate
  7. customPurify on 120 g silica gel with 1% MeOH/DCM

Sources & evidence

ORD record
ord-45901961ef0b4b54abc2b9607fa1e5b2
Source dataset
uspto-grants-2012_04
Patent number
US08148387B2

Reaction notes

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