Imidazole → methyl 2-(benzyloxy)-4-(1H-imidazol-1-yl)benzoate

HRID 454474Notes

Reaction equation

HRID 454474 reaction equation
[NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.N1CCC[C@@H]1C(O)=O.C(=O)([O-])[O-].[K+].[K+].[CH2:20]([O:27][C:28]1[CH:37]=[C:36](I)[CH:35]=[CH:34][C:29]=1[C:30]([O:32][CH3:33])=[O:31])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>[Cu]I.C(OCC)(=O)C.O.CS(C)=O>[CH2:20]([O:27][C:28]1[CH:37]=[C:36]([N:1]2[CH:5]=[CH:4][N:3]=[CH:2]2)[CH:35]=[CH:34][C:29]=1[C:30]([O:32][CH3:33])=[O:31])[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Participants

9

Reactant 4

HCID 795ImidazoleHCID 8988D-Proline2×HCID 11430Potassium CarbonateHCID 66990993Methyl 2-(benzyloxy)-4-iodobenzoate

Product 1

HCID 66990349methyl 2-(benzyloxy)-4-(1H-imidazol-1-yl)benzoateYield 77.6%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 679Dimethyl SulfoxideSolvent2×HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

1H-Imidazole (0.044 g), D-proline (0.013 g), potassium carbonate (0.15 g), and copper(I) iodide (0.010 g) were added to a dimethyl sulfoxide (1 mL) solution of methyl 2-(benzyloxy)-4-iodobenzoate (0.20 g), followed by stirring under a nitrogen atmosphere at 90° C. for 1 hour. The reaction mixture was cooled to room temperature, and then dimethyl sulfoxide (0.5 mL), D-proline (0.013 g), and copper(I) iodide (0.010 g) were added thereto, followed by stirring under a nitrogen atmosphere at 90° C. for 2 hours. After cooling the reaction mixture to room temperature, water and ethyl acetate were added thereto, and the insoluble substance was removed by filtration. The organic layer was separated, washed with water and a saturated aqueous solution of sodium chloride sequentially, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography [Fuji Silysia Chemical Ltd., PSQ100B (spherical), eluent: 90-20% hexane/ethyl acetate] to obtain 0.13 g of methyl 2-(benzyloxy)-4-(1H-imidazol-1-yl)benzoate as a white solid.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. stirringby stirring under a nitrogen atmosphere at 90° C. for 2 hours
  3. temperatureAfter cooling the reaction mixture to room temperature
  4. customthe insoluble substance was removed by filtration
  5. customThe organic layer was separated
  6. washwashed with water
  7. dry with materiala saturated aqueous solution of sodium chloride sequentially, and dried over anhydrous magnesium sulfate
  8. customthe solvent was evaporated under reduced pressure
  9. customThe obtained residue was purified by silica gel column chromatography [Fuji Silysia Chemical Ltd., PSQ100B (spherical), eluent: 90-20% hexane/ethyl acetate]

Sources & evidence

ORD record
ord-6d4c8d2be9d845b4897dc2a5858aa193
Source dataset
uspto-grants-2013_07
Patent number
US08492582B2

Reaction notes

Loading…