Reaction #1605777

Reaction equation

2-hydroxy-4-methyl-benzamide

K2CO3

Me2SO4

→

2-methoxy-4-methyl-benzamide

Solvents

acetone

Conditions

Workup

1. 1
   Temperaturewas heated
2. 2
   workup.ADDITIONwas added at that temperature
3. 3
   TemperatureThe resulting mixture was refluxed overnight
4. 4
   FiltrationThe reaction mixture was then filtered
5. 5
   Concentrationthe filtrate was concentrated
6. 6
   workup.DISSOLUTIONThe resulting residue was dissolved in 1000 mL of methanol/ammonia (1:1)
7. 7
   OtherAfter removal of the solvent
8. 8
   Otherthe residue was recrystallized from EtOAc/PE

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, 1 H), 6.81 (d, J=7.6 Hz, 1 H), 3.85 (s, 3H), 2.31 (s, 3H).

Source