Uses
2-Amino-5-fluorobenzoic acid methyl ester is used as an intermediate component in the preparation of hepatitis B virus (HBV) vaccines and quinazoline derivatives. It is also used in the synthesis of other organic heterocyclic compounds such as 2-aminobenzoates and α,β-unsaturated ketones.
Synthesis
General procedure for the synthesis of methyl 2-amino-5-fluorobenzoate from methanol and 2-amino-5-fluorobenzoic acid: 2-amino-5-fluorobenzoic acid (9.29 mmol, 1.440 g) was dissolved in 3N HCl/MeOH solution (30 mL), and heated to reflux at 100 °C overnight. Upon completion of the reaction, the solvent was removed by evaporation and the crude product was separated by extraction between dichloromethane (DCM) and saturated aqueous potassium carbonate (K2CO3). The organic phase was collected, evaporated and concentrated, and purified by silica gel (SiO2) column chromatography with hexane/ethyl acetate mixed solvent as eluent to give 0.650 g of methyl 2-amino-5-fluorobenzoate in 42% yield. The structure of the product was confirmed by 1H NMR (200 MHz, CDCl3): δ 3.9 (s, 3H), 5.6 (s, 2H), 6.6 (dd, J = 9.0, 4.7 Hz, 1H), 7.0 (m, 1H), 7.5 (dd, J = 9.8, 3.1 Hz, 1H). Mass spectrometry analysis (ESI/MS) showed the molecular ion peak m/z 170 [M+1]+.
References
[1] Patent: WO2009/21696, 2009, A1. Location in patent: Page/Page column 65-66
[2] Journal of Medicinal Chemistry, 2004, vol. 47, # 24, p. 5923 - 5936
[3] Chemistry of Heterocyclic Compounds, 2006, vol. 42, # 1, p. 64 - 69
[4] Journal of Heterocyclic Chemistry, 2010, vol. 47, # 2, p. 415 - 420
[5] Journal of Medicinal Chemistry, 2013, vol. 56, # 21, p. 8332 - 8338
