Methyl iodide → Methyl 2-methoxy-4-nitrobenzoate

HRID 32285Notes

Reaction equation

HRID 32285 reaction equation
[CH3:1][O:2][C:3](=[O:14])[C:4]1[CH:9]=[CH:8][C:7]([N+:10]([O-:12])=[O:11])=[CH:6][C:5]=1[OH:13].[H-].[Na+].[CH3:17]I>CN(C)C=O>[CH3:1][O:2][C:3](=[O:14])[C:4]1[CH:9]=[CH:8][C:7]([N+:10]([O-:12])=[O:11])=[CH:6][C:5]=1[O:13][CH3:17]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 139539Salicylic acid, 4-nitro-, methyl ester

Product 1

HCID 10798535Methyl 2-methoxy-4-nitrobenzoateYield 47.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

788 mg (4 mmol) of 2-hydroxy-4-nitro-benzoic acid methyl ester is mixed in 20 ml of absolute dimethylformamide with 177 mg of sodium hydride (60%; 4.4 mmol), and it is heated for 1 hour to 50° C. After cooling to room temperature, it is mixed with 625 mg (4.4 mmol) of methyl iodide and heated for 4 hours to a bath temperature of 80° C. After concentration by evaporation, it is taken up in 50 ml of water and extracted three times with 25 ml each of ethyl acetate. The ethyl acetate phase is washed with water, dried, filtered and concentrated by evaporation. The residue is chromatographed on 5 g of Isolute SI. (50 μm) with a gradient from cyclohexane to cyclohexane:ethyl acetate=80:20 as an eluant, and 400 mg (47% of theory) of 2-methoxy-4-nitro-benzoic acid methyl ester is obtained as an oil.

Workup

  1. temperatureis heated for 1 hour to 50° C
  2. temperatureheated for 4 hours to a bath temperature of 80° C
  3. concentrationAfter concentration
  4. customby evaporation, it
  5. extractionextracted three times with 25 ml each of ethyl acetate
  6. washThe ethyl acetate phase is washed with water
  7. customdried
  8. filtrationfiltered
  9. concentrationconcentrated by evaporation
  10. customThe residue is chromatographed on 5 g of Isolute SI

Sources & evidence

ORD record
ord-62d13e2339014fb69732efb087b22d28
Source dataset
uspto-grants-2008_09
Patent number
US07427390B2

Reaction notes

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