3-(5-(Trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoicacid

Synthesis

3-(N-hydroxyformamidinyl)benzoic acid (1 g, 5.6 mmol) was dissolved in anhydrous pyridine (15 mL) and cooled to 0 °C. Trifluoroacetic anhydride (2.3 mL, 16.7 mmol) was added slowly and dropwise. After the reaction mixture was gradually warmed to room temperature, it was further heated to 50 °C and the reaction was maintained for 3 hours. After completion of the reaction, the mixture was poured into ice water and the pH was adjusted to 4 with 1.5 N HCl. The product was extracted with EtOAc and concentrated under reduced pressure to remove the solvent. The crude product was purified by column chromatography (silica gel 60-120 mesh, eluent: 10% EtOAc/petroleum ether) to afford the target compound 3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoic acid (400 mg, 28% yield). The product was confirmed by 1H NMR (400 MHz, CDCl3): δ 13.44 (br s, 1H), 8.56 (s, 1H), 8.30 (d, J=7.9 Hz, 1H), 8.21 (d, J=7.9 Hz, 1H), 7.78 (t, J=7.8 Hz, 1H). Mass spectrometry (ESI) analysis: m/z calculated value of C10H5F3N2O3 was 258.03; measured value 257 (M-H).

References

[1] Patent: WO2013/6408, 2013, A1. Location in patent: Page/Page column 39; 40
[2] Patent: EP2533783, 2015, B1. Location in patent: Paragraph 0136-0137
[3] Patent: WO2017/112838, 2017, A1. Location in patent: Paragraph 87