Potassium Carbonate → 2-(5-(3,4-dimethoxy-5-nitrophenyl)-1H-imidazol-1-yl)-5-(trifluoromethyl)pyridine

HRID 42650

Reaction equation

HRID 42650 reaction equation
[F:1][C:2]([F:11])([F:10])[C:3]1[CH:4]=[CH:5][C:6]([NH2:9])=[N:7][CH:8]=1.[CH3:12][O:13][C:14]1[CH:15]=[C:16]([CH:19]=[C:20]([N+:24]([O-:26])=[O:25])[C:21]=1[O:22][CH3:23])[CH:17]=O.[N+:27]([CH2:29]S(C1C=CC(C)=CC=1)(=O)=O)#[C-:28].C(=O)([O-])[O-].[K+].[K+]>C(O)C.C(O)(=O)C.CO.COCCOC>[CH3:12][O:13][C:14]1[CH:15]=[C:16]([C:17]2[N:9]([C:6]3[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:10])[F:11])=[CH:8][N:7]=3)[CH:29]=[N:27][CH:28]=2)[CH:19]=[C:20]([N+:24]([O-:26])=[O:25])[C:21]=1[O:22][CH3:23]

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 161915Tosylmethyl isocyanideHCID 7358622-Amino-5-(trifluoromethyl)pyridineHCID 108675653,4-Dimethoxy-5-nitrobenzaldehyde

Product 1

HCID 687019682-(5-(3,4-dimethoxy-5-nitrophenyl)-1H-imidazol-1-yl)-5-(trifluoromethyl)pyridine

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 887MethanolSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a stirred solution of 5-(trifluoromethyl)pyridin-2-amine (0.405 g, 2.5 mmol) in a mixture of ethanol (12.5 mL) and acetic acid (0.25 mL) at room temperature was added 3,4-dimethoxy-5-nitrobenzaldehyde (0.53 g, 2.5 mmol). The reaction was heated at reflux temperature for two hours then ethanol was evaporated. The oily residue was dissolved in a mixture of methanol (17 mL) and 1,2-dimethoxyethane (7.5 mL), whereupon 1-(isocyanomethylsulfonyl)-4-methylbenzene (TOSMIC) (0.73 g, 3.75 mmol) and potassium carbonate (0.69 g, 5 mmol) were added in one portion. The resulting mixture was stirred at reflux temperature for 3 hours. The reaction was evaporated to dryness, and then taken up in dichloromethane (50 ml). The organic phase was washed with water (50 mL) and then dried over anhydrous magnesium sulphate, filtered and evaporated to leave brown oil. Column chromatography over silica gel (petroleum ether-ethyl acetate 9:1) gave 2-(5-(3,4-dimethoxy-5-nitrophenyl)-1H-imidazol-1-yl)-5-(trifluoromethyl)pyridine, 0.542 g (55%).

Workup

  1. temperatureThe reaction was heated
  2. temperatureat reflux temperature for two hours
  3. customethanol was evaporated
  4. additionwere added in one portion
  5. temperatureat reflux temperature for 3 hours
  6. customThe reaction was evaporated to dryness
  7. washThe organic phase was washed with water (50 mL)
  8. dry with materialdried over anhydrous magnesium sulphate
  9. filtrationfiltered
  10. customevaporated
  11. customto leave brown oil

Sources & evidence

ORD record
ord-5fe24992b3e64f0c88110d47cb693837
Source dataset
uspto-grants-2013_09
Patent number
US08536203B2

Linked notes

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