Sulfuric Acid → ethyl 8-(1H-1,2,4-triazol-1-yl)-6-(trifluoromethyl)imidazo[1,2-a]pyridine-3-carboxylate

HRID 931046Notes

Reaction equation

HRID 931046 reaction equation
[N:1]1([C:6]2[C:7]([NH2:16])=[N:8][CH:9]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:11]=2)[CH:5]=[N:4][CH:3]=[N:2]1.Cl[C:18]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:19][O-].[K+].S(=O)(=O)(O)O>C(O)C>[N:1]1([C:6]2[C:7]3[N:8]([C:18]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:19][N:16]=3)[CH:9]=[C:10]([C:12]([F:13])([F:15])[F:14])[CH:11]=2)[CH:5]=[N:4][CH:3]=[N:2]1

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 74089075Potassium 2-chloro-3-ethoxy-3-oxoprop-1-en-1-olateHCID 1183789173-(1H-1,2,4-triazol-1-yl)-5-(trifluoromethyl)pyridin-2-amine

Product 1

HCID 118379016ethyl 8-(1H-1,2,4-triazol-1-yl)-6-(trifluoromethyl)imidazo[1,2-a]pyridine-3-carboxylateYield 65.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 3-(1H-1,2,4-triazol-1-yl)-5-(trifluoromethyl)pyridin-2-amine (2.4 g), potassium 2-chloro-3-ethoxy-3-oxoprop-1-en-1-olate (4.54 g), sulfuric acid (0.670 mL) and ethanol (100 mL) was heated with reflux for 3 days. The reaction mixture was concentrated under reduced pressure, ethyl acetate was added thereto, and the mixture was washed with water. The aqueous layer was neutralize with saturated aqueous sodium bicarbonate solution, and extracted with ethyl acetate. The organic layers were combined, washed with water and saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane), and the obtained solid was recrystallized from ethyl acetate/hexane to give the title compound (2.22 g).

Workup

  1. temperaturewas heated
  2. temperaturewith reflux for 3 days
  3. concentrationThe reaction mixture was concentrated under reduced pressure, ethyl acetate
  4. additionwas added
  5. washthe mixture was washed with water
  6. extractionextracted with ethyl acetate
  7. washwashed with water and saturated brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. customthe solvent was evaporated under reduced pressure
  10. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)
  11. customthe obtained solid was recrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-8e7b2229115e49789ed03b71f80310b8
Source dataset
uspto-grants-2016_03
Patent number
US09296746B2

Reaction notes

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