Dimethylformamide → 4-(4-{2-butyl-1-[4-(4-fluoro-3-trifluoromethyl-phenoxy)-phenyl]-1H-imidazol-4-yl}-phenoxy)-1-methyl-piperidine

HRID 17656

Reaction equation

HRID 17656 reaction equation
[F:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][C:7]2[CH:13]=[CH:12][C:10]([NH2:11])=[CH:9][CH:8]=2)=[CH:4][C:3]=1[C:16]([F:19])([F:18])[F:17].[CH3:20][N:21]([CH:23]=O)[CH3:22].Br[CH2:26][C:27]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=O>O.CCOCC>[CH2:9]([C:10]1[N:11]([C:10]2[CH:9]=[CH:8][C:7]([O:6][C:5]3[CH:14]=[CH:15][C:2]([F:1])=[C:3]([C:16]([F:17])([F:18])[F:19])[CH:4]=3)=[CH:13][CH:12]=2)[CH:26]=[C:27]([C:29]2[CH:34]=[CH:33][C:32]([O:6][CH:5]3[CH2:14][CH2:22][N:21]([CH3:20])[CH2:23][CH2:4]3)=[CH:31][CH:30]=2)[N:11]=1)[CH2:8][CH2:7][CH3:13]

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 6259Phenacyl bromideHCID 669773444-[4-Fluoro-3-(trifluoromethyl)phenoxy]aniline

Product 1

HCID 596993654-(4-{2-butyl-1-[4-(4-fluoro-3-trifluoromethyl-phenoxy)-phenyl]-1H-imidazol-4-yl}-phenoxy)-1-methyl-piperidine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Procedure

To a stirred solution of 4-(4-fluoro-3-trifluoromethyl-phenoxy)-aniline (1.64 mmol) in anhydrous DMF (30 mL) DIEA (3 eq) was added, followed by slow addition of the alpha-bromoacetophenone described above (2 eq), according to General Procedure R2. The reaction mixture was stirred under nitrogen at rt until completion, as indicated by TLC and HPLC. The reaction mixture was then diluted with cold H2O and the product was isolated in Et2O. The combined organic layers were washed with brine and dried over sodium sulfate. Evaporation of solvent in vacuuo afforded the desired product. The crude alkylated aniline was purified by chromatography on silica gel (elution with 5-20% EtOAc/Hexane).

Workup

  1. washThe combined organic layers were washed with brine
  2. dry with materialdried over sodium sulfate
  3. customEvaporation of solvent in vacuuo

Sources & evidence

ORD record
ord-a3c4b57671024732b848cf03e61f3468
Source dataset
uspto-grants-2010_06
Patent number
US07737285B2

Linked notes

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