4-Fluoro-3-methylbenzoic acid

White to light yellow crystal powder

4-Fluoro-3-methylbenzoic acid serves as a precursor for ester derivatives: it is esterified with isobutylene under catalytic trifluoromethanesulfonic acid to give the tert-butyl ester in 94% yield, and with methanol and concentrated sulfuric acid under reflux to give methyl 4-fluoro-3-methylbenzoate in 98% yield[1][2].

Journal of Medicinal Chemistry, 21, p. 38, 1978 DOI: 10.1021/jm00199a007

[1]Källström, S., & Leino, R. (2008). Synthesis of pharmaceutically active compounds containing a disubstituted piperidine framework. Bioorganic & Medicinal Chemistry, 16(2), 601–635. https://doi.org/10.1016/j.bmc.2007.10.018
[2]Waldschmidt, H. V., Homan, K. T., Cruz-Rodríguez, O., Cato, M. C., Waninger-Saroni, J., Larimore, K. M., Cannavo, A., Song, J., Cheung, J. Y., Kirchhoff, P. D., Koch, W. J., Tesmer, J. J. G., & Larsen, S. D. (2016). Structure-Based Design, Synthesis, and Biological Evaluation of Highly Selective and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors. Journal of Medicinal Chemistry, 59(8), 3793–3807. https://doi.org/10.1021/acs.jmedchem.5b02000