3-Bromo-5-fluoropyridine

Chemical Properties

Colorless liquid

Uses

3-Bromo-5-fluoropyridine reacts with silylformamidine to afford aminals[3]. It serves as a starting material for the synthesis of 3-(benzylthio)-5-bromopyridine[4].

Synthesis

Step 2: Synthesis of 3-bromo-5-fluoropyridine To a cooled solution of 10.0 g (0.058 mol) of 3-amino-5-bromopyridine dissolved in 59 mL of 50% tetrafluoroboric acid was added dropwise at -10 °C a solution prepared from 4.19 g (0.06 mol) of sodium nitrite dissolved in 13 mL of water. The reaction mixture was stirred at -8°C for 1 hr and then 150 mL of ether was added. The crude diazonium salt was collected by filtration and washed with ether. Subsequently, the crude diazonium salt was added in batches to 200 mL of toluene preheated to 80°C. The reaction mixture was stirred at 90°C for 1 hour and then the organic phase was concentrated. The light yellow residue was suspended in 150 mL of water and the pH was adjusted with 32% sodium hydroxide solution to 11. The aqueous phase was extracted three times with 200 mL of dichloromethane. The organic phases were combined, washed with water, dried over magnesium sulfate, and concentrated. The crude product was purified by vacuum distillation (10 mbar, 35 °C) to give 15.4 g of brown oil, which was further purified to give 5.6 g (0.032 mol, 55% yield) of the target compound 3-bromo-5-fluoropyridine as a colorless oil (ISP): m/e = 176.1, 178.1 (M + H+).

References

[1] Patent: US2006/199960,  2006,  A1. Location in patent: Page/Page column 21
[2] Recueil des Travaux Chimiques des Pays-Bas,  1955,  vol. 74,  p. 1062,1068
[3] Koidan, G., Zahorulko, S., Hurieva, A., Shvydenko, T., Rusanov, E. B., Rozhenko, A. B., Manthe, U., & Kostyuk, A. (2023). Straightforward Synthesis of Halopyridine Aldehydes via Diaminomethylation. Chemistry – A European Journal, 29(55). https://doi.org/10.1002/chem.202301675
[4] Cherepakha, A. Y., Stepannikova, K. O., Vashchenko, B. V., Gorichko, M. V., Tolmachev, A. A., & Grygorenko, O. O. (2018). Hetaryl Bromides Bearing the SO2F Group – Versatile Substrates for Palladium‐Catalyzed C–C Coupling Reactions. European Journal of Organic Chemistry, 2018(47), 6682–6692. https://doi.org/10.1002/ejoc.201801270