Dimethyl Sulfate → 2-Methoxy-4-methylbenzamide

HRID 1881802Notes

Reaction equation

HRID 1881802 reaction equation
[OH:1][C:2]1[CH:10]=[C:9]([CH3:11])[CH:8]=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].[C:12]([O-])([O-])=O.[K+].[K+].COS(OC)(=O)=O>CC(C)=O>[CH3:12][O:1][C:2]1[CH:10]=[C:9]([CH3:11])[CH:8]=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5]

Participants

5

Reactant 3

HCID 6497Dimethyl SulfateHCID 11430Potassium CarbonateHCID 105348392-Hydroxy-4-methylbenzamide

Product 1

HCID 219473972-Methoxy-4-methylbenzamideYield 617.5%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A mixture of 2-hydroxy-4-methyl-benzamide (15.1 g, 0.1 mol) and K2CO3 (41.7 g, 0.3 mol) in 1000 mL of acetone was heated to reflux for 1 hour before Me2SO4 was added at that temperature. The resulting mixture was refluxed overnight. The reaction mixture was then filtered and the filtrate was concentrated. The resulting residue was dissolved in 1000 mL of methanol/ammonia (1:1) and stirred at room temperature for 3 hours. After removal of the solvent, the residue was recrystallized from EtOAc/PE to afford 102 g of 2-methoxy-4-methyl-benzamide (yield 61%). 1H NMR (400 MHz, DMSO-d6): δ 7.72 (d, J=7.6 Hz, 1H), 7.57 (br s, 1H), 7.46 (br s, 1H), 6.92 (s, 1H), 6.81 (d, J=7.6 Hz, 1H), 3.85 (s, 3H), 2.31 (s, 3H).

Workup

  1. temperaturewas heated
  2. additionwas added at that temperature
  3. temperatureThe resulting mixture was refluxed overnight
  4. filtrationThe reaction mixture was then filtered
  5. concentrationthe filtrate was concentrated
  6. dissolutionThe resulting residue was dissolved in 1000 mL of methanol/ammonia (1:1)
  7. customAfter removal of the solvent
  8. customthe residue was recrystallized from EtOAc/PE

Sources & evidence

ORD record
ord-96db5cabd17044b9ace8936bd07f9758
Source dataset
uspto-grants-2012_11
Patent number
US08318947B2

Reaction notes

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