Aniline → Ethyl 2,5-dimethyl-1-phenyl-1H-imidazole-4-carboxylate

HRID 75490Notes

Reaction equation

HRID 75490 reaction equation
[C:1]([NH:4][CH:5]([C:11](=O)[CH3:12])[C:6]([O:8][CH2:9][CH3:10])=[O:7])(=O)[CH3:2].[NH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.FC(F)(F)C(O)=O>C(#N)CCC>[CH3:2][C:1]1[N:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:11]([CH3:12])=[C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])[N:4]=1

Participants

5

Reactant 3

HCID 6115Aniline2×HCID 6422Trifluoroacetic acidHCID 224840Ethyl 2-acetamido-3-oxobutanoate2×

Product 1

HCID 54579220Ethyl 2,5-dimethyl-1-phenyl-1H-imidazole-4-carboxylateYield 76.2%

Reagents, catalysts & solvents 1

HCID 8008ButyronitrileSolvent

Procedure

To a solution of ethyl 2-acetamido-3-oxobutanoate (compound 10, 5.0 g, 26.7 mmol), aniline (compound 11a, 7.3 mL, 80.1 mmol) in butyronitrile (10 mL) was added trifluoroacetic acid (6.2 mL, 80.1 mmol) at room temperature. The reaction mixture was irradiated in a microwave reactor (Biotage Initiator™) for 40 minutes at 140° C. The mixture was concentrated under reduced pressure. The residue was diluted with CH2Cl2, and washed with aqueous K2CO3. The organic layer was dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The crude product was purified by flash column chromatography (Biotage SP1™ FLASH Purification System was used for normal phase column chromatography with tetrahydrofuran and hexane) to provide the title compound (4.97 g, 76%) as a yellow solid.

Workup

  1. customThe reaction mixture was irradiated in a microwave reactor (Biotage Initiator™) for 40 minutes at 140° C
  2. concentrationThe mixture was concentrated under reduced pressure
  3. additionThe residue was diluted with CH2Cl2
  4. washwashed with aqueous K2CO3
  5. dry with materialThe organic layer was dried over anhydrous MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by flash column chromatography (Biotage SP1™ FLASH Purification System was used for normal phase column chromatography with tetrahydrofuran and hexane)

Sources & evidence

ORD record
ord-87a761685bdf421fa9130da93c9e6a9b
Source dataset
uspto-grants-2014_09
Patent number
US08835436B2

Reaction notes

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