Reaction #1605771

Reaction equation

2-hydroxy-4-methylbenzoic acid

K2CO3

KOH

HCl

→

2-methoxy-4-methylbenzoic acid

Solvents

acetone

MeOH

Conditions

Workup

1. 1
   Temperaturethe reaction mixture heated
2. 2
   Temperatureat reflux for 48 hrs
3. 3
   Filtrationwas filtered
4. 4
   Otherthe filtrate was evaporated
5. 5
   Otherto give the crude methyl 2-methoxy-4-methylbenzoate
6. 6
   Temperaturethe solution heated
7. 7
   Temperatureat reflux 48 hrs
8. 8
   TemperatureAfter cooling the reaction mixture
9. 9
   Extractionextracted with ethyl acteate
10. 10
    WashThe organic layer was washed with brine
11. 11
    Dryingdried over MgSO4
12. 12
    Filtrationfiltered
13. 13
    Otherevaporated
14. 14
    OtherThe residue was triturated with Ethyl acetate/Hexane

Procedure

To a solution of 2-hydroxy-4-methylbenzoic acid (25 g, 0.164 mol) in acetone (350 mL) was added K2CO3 (68 g, 0.492 mmol) followed by MeI (41 mL, 0.656 mmol) and the reaction mixture heated at reflux for 48 hrs. After cooling to r.t. the reaction mixture was filtered and the filtrate was evaporated to give the crude methyl 2-methoxy-4-methylbenzoate. KOH (11.3 g, 1.2 eq) was dissolved in MeOH (300 mL) and the crude ester was added to the mixture and the solution heated at reflux 48 hrs. After cooling the reaction mixture was acidified with aq. HCl (1N) and extracted with ethyl acteate. The organic layer was washed with brine, dried over MgSO4, filtered and evaporated. The residue was triturated with Ethyl acetate/Hexane to give 20 g of 2-methoxy-4-methylbenzoic acid as a cream white solid (85% yield)

Source