Synthesis
General Steps:
1. 1.9 g (15.3 mmol) of 3,5-dimethylfluorobenzene was dissolved in a solvent mixture of about 13.5 mL of pyridine and about 9.5 mL of water under mild reflux conditions.
2. 13.8 g (87.3 mmol) of potassium permanganate (KMnO4) was added to the above solution in batches.
3. The reaction mixture was refluxed for about 7 hours to ensure complete reaction.
4. Upon completion of the reaction, an appropriate amount of sodium sulfite was added to quench the unreacted potassium permanganate.
5. Filter the reaction mixture while hot to remove insoluble impurities. 6.
6. To the filtrate, 1N hydrochloric acid (HCl) was slowly added to adjust the pH to 3. 7.
7. The filtrate was washed with ethyl acetate (EtOAc) and subsequently saturated with sodium chloride (NaCl).
8. The aqueous phase was extracted 3-4 times using a solvent mixture consisting of 80 mL of chloroform (CHCl3), 10 mL of methanol (MeOH) and 10 mL of water (H2O).
9. All organic extracts were combined and dried with anhydrous sodium sulfate.
10. The dried organic phase was filtered and the filtrate was concentrated to give about 400 mg (14% yield) of 5-fluoroisophthalic acid as a light yellow solid.
References
[1] Patent: WO2006/110668, 2006, A1. Location in patent: Page/Page column 55; 60
[2] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1984, # 3, p. 529 - 532
[3] Patent: US2003/181334, 2003, A1
