Uses
3-Bromo-2,5-dichloropyridine acts as a precursor that reacts with n-BuLi and is treated with 3(R)-(tert-butyldimethylsiloxy)butyraldehyde to yield 3-[3(R)-(tert-butyldimethylsiloxy)-1-hydroxybutyl]-2,5-dichloropyridine, and undergoes transmetalation using isopropyl ether to obtain 2,5-dichloro-3-lithiopyridine[2].
Synthesis
Example 3 Synthesis of 3-bromo-2,5-dichloropyridine: To a solution of 3-bromo-5-chloropyridin-2-one (84.3 g, 0.404 mol) in N,N-dimethylformamide (DMF, 100 mL) was slowly added phosphorus oxychloride (POCl3, 56.5 mL, 0.61 mol) through a dropping funnel at room temperature, and the process of dropping was continued for 3 hours. Subsequently, the resulting black solution was heated to 70 °C and the reaction was stirred at this temperature for 3 days. Upon completion of the reaction, the mixture was cooled to room temperature and carefully poured into 1 L of ice water. The precipitated solid was collected by filtration and dried in a vacuum oven to afford 81.76 g (89% yield) of the target product 3-bromo-2,5-dichloropyridine as a white solid with a melting point of 39-41 °C. The product was confirmed by infrared spectroscopy (IR, CHCl3), and the main absorption peaks were located at 3867, 3663, 2989, 2734, 1812, 1606, 1547, 1400, 1366, 1230, 1155, 1129, 1074, 1027, 894, 658, and 563 cm-1. Nuclear magnetic resonance hydrogen spectroscopy (1H NMR, 300 MHz, CDCl3) showed signals at δ 8.0 (d, 1H, J = 2.2 Hz) and 8.35 (d, 1H, J = 2.2 Hz). Nuclear magnetic resonance carbon spectra (13C NMR, CDCl3) showed signals at δ 120.43, 130.74, 141.46, 146.64, and 148.99. The high resolution mass spectrum measured the molecular weight of 224.8764, which is consistent with the calculated value of C5H2NBrCl2 (224.8748).
References
[1] Patent: US5068333, 1991, A
[2] Murtiashaw, C. W., Breitenbach, R., Goldstein, S. W., Pezzullo, S. L., Quallich, G. J., & Sarges, R. (1992). 2,3-Pyridine annulation. The enantioselective synthesis of an aldose reductase inhibitor. The Journal of Organic Chemistry, 57(6), 1930–1933.
https://doi.org/10.1021/jo00032a060
