Uses
2,6-Difluoro-3-nitrobenzoic acid is a benzoic acid derivative that contains reactive substituent fluorine atoms and nitro groups in its molecular structure. The substance is mainly used as a reagent for organic synthesis or as a component of pharmaceutical intermediates. It is used in the synthesis of B-Raf kinase inhibitors, such as vemurafenib, which causes programmed cell death (apoptosis) in melanoma cell lines. In addition, it is used in the synthesis of fluoroquinolone antibacterial agents.
Synthesis
General procedure for the synthesis of 2,6-difluoro-3-nitrobenzoic acid from 2,6-difluorobenzoic acid: Concentrated sulfuric acid (5 mL) was slowly added to 2,6-difluorobenzoic acid (1.4 g, 9 mmol) at 0 °C, followed by gradual addition of potassium nitrate (1 g, 9.9 mmol). After warming the reaction mixture to room temperature, stirring was continued for 24 hours. After completion of the reaction, ice water was poured into the reaction mixture and extracted with ethyl acetate. The organic layer was dried with anhydrous magnesium sulfate and subsequently concentrated under reduced pressure. The solid in the concentrated filtrate was washed with ether and dried to give 2,6-difluoro-3-nitrobenzoic acid (1.3 g, yield: 71%). The product was characterized by 1H NMR (400 MHz, DMSO-d6): δ 8.37 (td, J = 9.2,5.6 Hz, 1H), 7.46 (t, J = 9.2 Hz, 1H).
References
[1] Bioorganic and Medicinal Chemistry, 1999, vol. 7, # 11, p. 2647 - 2666
[2] Chemical and Pharmaceutical Bulletin, 1982, vol. 30, # 10, p. 3530 - 3543
[3] Journal of Medicinal Chemistry, 2003, vol. 46, # 10, p. 1905 - 1917
[4] Synlett, 2012, vol. 23, # 7, p. 1039 - 1042
[5] Patent: EP2647637, 2013, A2. Location in patent: Paragraph 0055
