Synthesis
General procedure for the synthesis of 2,3-difluoro-6-methoxybenzoic acid from 2,3-difluoro-6-methoxybenzaldehyde:
1. Preparation of reaction system: 2,3-difluoro-6-methoxybenzaldehyde (0.5 g, 2.91 mmol) was suspended in potassium hydroxide solution (3 g KOH dissolved in 20 ml of water).
2. Oxidizing reaction: hydrogen peroxide solution (27.5% w/w, 4 ml) was added to the above suspension, followed by heating the reaction at 70°C for 2 hours.
3. Acidification: after completion of the reaction, the reaction mixture was acidified to pH 2 with concentrated hydrochloric acid.
4. Extractive separation: the acidified reaction mixture was washed with ethyl acetate.
5. Drying and concentration: the organic phases were combined, dried with anhydrous magnesium sulfate, filtered and the solvent was evaporated in vacuum.
6. Purification: Further purification by azeotropy with toluene afforded 2,3-difluoro-6-methoxybenzoic acid as a white solid (500 mg, 91% yield).
Remarks: LC/MS analysis showed a retention time of 12.08 min and no molecular ion peak was observed.
References
[1] Patent: WO2006/77414, 2006, A1. Location in patent: Page/Page column 148
[2] Patent: CN105523921, 2016, A. Location in patent: Paragraph 0014; 0015; 0016
