Water → Ethyl 1-benzyl-5-methyl-1H-imidazole-4-carboxylate

HRID 1428984Notes

Reaction equation

HRID 1428984 reaction equation
[CH3:1][C:2]1[N:3]=[CH:4][NH:5][C:6]=1[C:7]([O:9][CH2:10][CH3:11])=[O:8].[H-].[Na+].[CH2:14](Br)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.O>C1COCC1>[CH2:14]([N:3]1[C:2]([CH3:1])=[C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[N:5]=[CH:4]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

6

Reactant 4

HCID 962WaterHCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 178470400HCID 178470400, compound

Product 1

HCID 13896233Ethyl 1-benzyl-5-methyl-1H-imidazole-4-carboxylateYield 47%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Part A: To a magnetically stirred suspension of ethyl 4-methyl-1H-imidazole-5-carboxylate (15.42 gram, 0.100 mol) in anhydrous THF was slowly added sodium hydride (NaH) (4.88 g of a 60% suspension, 0.120 mol) and the resulting mixture was stirred at room temperature for 30 minutes. Benzyl bromide (13.8 ml, 0.120 mol) was slowly added and the resulting mixture was reacted for 16 hours. Water was added to the mixture. The organic layer was separated from the water layer. The water layer was extracted 3 times with ethylacetate. The organic layer was dried over MgSO4, filtered and thoroughly concentrated to give an oil. The resulting residue was purified (in order to separate the two formed regioisomers) by flash chromatography (diethyl ether/ethyl acetate gradient) to give ethyl N-benzyl-5-methyl-1H-imidazole-4-carboxylate (11.4 gram, 47% yield). 1H-NMR (400 MHz, CDCl3): 1.40 (t, J=7, 3H), 2.45 (s, 3H), 4.37 (q, J=7, 2H), 5.10 (s, 2H), 7.03-7.08 (m, 2H), 7.28-7.38 (m, 3H), 7.48 (s, 1H).

Workup

  1. customthe resulting mixture was reacted for 16 hours
  2. customThe organic layer was separated from the water layer
  3. extractionThe water layer was extracted 3 times with ethylacetate
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationthoroughly concentrated
  7. customto give an oil
  8. customThe resulting residue was purified (in order
  9. customto separate the two formed regioisomers) by flash chromatography (diethyl ether/ethyl acetate gradient)

Sources & evidence

ORD record
ord-0bb24258a3f642dea2e664cfb22628d7
Source dataset
uspto-grants-2015_01
Patent number
US08937184B2

Reaction notes

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