5-Fluoro-2-hydroxybenzonitrile

Synthesis

5-Fluoro-2-hydroxybenzaldehyde oxime (920 mg, 5.93 mmol) was used as a raw material and dissolved in acetic anhydride (15 mL). Subsequently, a solution consisting of KOH (2 g) dissolved in H2O (10 mL) and ethanol (10 mL) was added to the mixture. The reaction mixture was heated at 80 °C for 2 h, after which it was cooled to room temperature. The pH of the reaction solution was adjusted to 7 with 6N HCl and then extracted twice with a solvent mixture of isopropanol/dichloromethane (1:3, v/v). The organic layers were combined and dried with anhydrous sodium sulfate. The resulting residue was purified by silica gel column chromatography using hexane/ethyl acetate (5:1, v/v) as eluent to afford the target product 2-hydroxy-5-fluorobenzonitrile (800 mg, 100% yield). The mass spectrum (DCI/NH3) showed m/z 136 (M + 1)+. 1H NMR (500 MHz, DMSO-d6) δ ppm: 6.99 (dd, J = 9.05, 4.37 Hz, 1H), 7.36 (td, J = 9.05, 3.12 Hz, 1H), 7.53 (dd, J = 8.42, 3.43 Hz, 1H). 11.04 (m, 1H).

References

[1] Patent: WO2005/111003, 2005, A1. Location in patent: Page/Page column 131
[2] Patent: EP2258697, 2010, A1. Location in patent: Page/Page column 40
[3] Patent: CN107778216, 2018, A. Location in patent: Paragraph 0023; 0024
[4] Patent: CN107778215, 2018, A. Location in patent: Paragraph 0023; 0024