Ethyl Acetate → methyl 2-methyl-3-nitro-4-[2-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-1-yl]benzoate

HRID 1189470Notes

Reaction equation

HRID 1189470 reaction equation
[O:1]1[CH2:6][CH2:5][CH:4]([C:7]2[NH:8][CH:9]=[CH:10][N:11]=2)[CH2:3][CH2:2]1.[H-].[Na+].F[C:15]1[CH:24]=[CH:23][C:18]([C:19]([O:21][CH3:22])=[O:20])=[C:17]([CH3:25])[C:16]=1[N+:26]([O-:28])=[O:27].C(OCC)(=O)C>CN(C)C=O.O>[CH3:25][C:17]1[C:16]([N+:26]([O-:28])=[O:27])=[C:15]([N:11]2[CH:10]=[CH:9][N:8]=[C:7]2[CH:4]2[CH2:3][CH2:2][O:1][CH2:6][CH2:5]2)[CH:24]=[CH:23][C:18]=1[C:19]([O:21][CH3:22])=[O:20]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 58575232Methyl 4-fluoro-2-methyl-3-nitrobenzoateHCID 591985872-(oxan-4-yl)-1H-imidazole

Product 1

HCID 58575597methyl 2-methyl-3-nitro-4-[2-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-1-yl]benzoateYield 96.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

To a mixed liquid of 1.70 g of 2-(tetrahydro-2H-pyran-4-yl)-1H-imidazole and 20.0 mL of N,N-dimethylformamide was added slowly 450 mg of 60% sodium hydride portionwise under ice-cooling, followed by stirring at the same temperature for 10 minutes and then stirring at room temperature for 30 minutes. After ice-cooling again, a mixed liquid of 2.00 g of methyl 4-fluoro-2-methyl-3-nitrobenzoate in 10.0 mL of N,N-dimethylformamide was added thereto, followed by stirring at the same temperature for 10 minutes and then stirring at room temperature overnight. To the reaction liquid were added ethyl acetate and water, followed by extraction with ethyl acetate, the organic layer was washed with water, a saturated aqueous sodium hydrogen carbonate solution, and saturated brine, and dried over anhydrous magnesium sulfate, and then the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform/methanol) to obtain 3.13 g of methyl 2-methyl-3-nitro-4-[2-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-1-yl]benzoate as a pale yellow solid.

Workup

  1. temperaturecooling
  2. stirringstirring at room temperature for 30 minutes
  3. temperatureAfter ice-cooling again
  4. stirringby stirring at the same temperature for 10 minutes
  5. stirringstirring at room temperature overnight
  6. customTo the reaction liquid
  7. extractionfollowed by extraction with ethyl acetate
  8. washthe organic layer was washed with water
  9. dry with materiala saturated aqueous sodium hydrogen carbonate solution, and saturated brine, and dried over anhydrous magnesium sulfate
  10. customthe solvent was evaporated under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (chloroform/methanol)

Sources & evidence

ORD record
ord-284cdfa83e1a4d64b98d76bc6cc65ba2
Source dataset
uspto-grants-2014_03
Patent number
US08674096B2

Reaction notes

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