4-Chlorobenzaldehyde → 4-[5-(4-tert-Butyl-phenyl)-2-(4-chloro-phenyl)-3H-imidazol-4-yl]-pyridine

HRID 1418053Notes

Reaction equation

HRID 1418053 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]([CH:13]([C:22]2[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=2)O[Si](C(C)(C)C)(C)C)=O)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C([O-])(=O)C.[NH4+:32].[Cl:33][C:34]1[CH:41]=[CH:40][C:37]([CH:38]=O)=[CH:36][CH:35]=1.[OH-].[NH4+:43]>C(O)(=O)C.C([O-])(=O)C.[Cu+2].C([O-])(=O)C.C(OCC)(=O)C>[C:1]([C:5]1[CH:6]=[CH:7][C:8]([C:11]2[N:32]=[C:38]([C:37]3[CH:40]=[CH:41][C:34]([Cl:33])=[CH:35][CH:36]=3)[NH:43][C:13]=2[C:22]2[CH:23]=[CH:24][N:25]=[CH:26][CH:27]=2)=[CH:9][CH:10]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 4

HCID 77264-ChlorobenzaldehydeHCID 14923Ammonium HydroxideHCID 517165Ammonium AcetateHCID 674868814-Pyridyl-t-butydimethylsilyloxymethyl 4-t-butylphenyl ketone

Product 1

HCID 98432394-[5-(4-tert-Butyl-phenyl)-2-(4-chloro-phenyl)-3H-imidazol-4-yl]-pyridineYield 59%

Reagents, catalysts & solvents 3

HCID 8895Cupric acetateCatalystHCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 4-pyridyl-t-butydimethylsilyloxymethyl 4-t-butylphenyl ketone from Step C (170 mg, 0.44 mmol), copper (II) acetate (161 mg, 0.89 mmol), ammonium acetate (342 mg, 4.44 mmol) and 4-chlorobenzaldehyde (78 mg, 0.56 mmol) in acetic acid (3 mL) was heated to 110° C. for 5 h. The reaction mixture was then cooled to 0° C. and ice (4 g), ethyl acetate (4 mL) and concentrated ammonium hydroxide solution (4 mL) were added. After stirring for 30 min, the phases were separated and the aqueous layer extracted with ethyl acetate (2 times). The combined organic phases were successively washed with water (2 times) and saturated salt solution and dried over anhydrous sodium sulfate. The mixture was filtered and the solvent removed by rotoevaporation. The residue was purified by flash column chromatography on silica gel eluted with 0-3% methanol in methylene chloride to yield the title compound as a pale yellow solid 102 mg, 59% yield), mass spectrum (CI) m/e=388 (M+1)+.

Workup

  1. customthe phases were separated
  2. extractionthe aqueous layer extracted with ethyl acetate (2 times)
  3. washThe combined organic phases were successively washed with water (2 times) and saturated salt solution
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationThe mixture was filtered
  6. customthe solvent removed by rotoevaporation
  7. customThe residue was purified by flash column chromatography on silica gel
  8. washeluted with 0-3% methanol in methylene chloride

Sources & evidence

ORD record
ord-8d4e00615b9a4d69934dcbf35ea0d131
Source dataset
uspto-grants-1999_03
Patent number
US05880139

Reaction notes

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