Uses
3-Acetyl-2-chloropyridine is a reagent used in the synthesis of Volitinib, a highly potent and selective mesenchymal-epithelial transition factor (c-Met) inhibitor as an anti-cancer agent.
Synthesis
Step 2: Synthesis of 1-(2-chloropyridin-3-yl)ethanone
1-(2-Chloropyridin-3-yl)ethanol (10 g, 0.0635 mol) was dissolved in anhydrous acetone (200 mL), transferred to a 1-liter flask and the reaction was carried out under argon protection. The reaction mixture was cooled to -30 °C, followed by slow addition of pure crushed chromic anhydride (19 g, 0.19 mol). The reaction mixture was stirred at room temperature for 3 hours. Upon completion of the reaction, 2-propanol (100 mL) was added to quench the reaction, followed by adjusting the pH with aqueous sodium bicarbonate to 8. The reaction mixture was filtered and the solid was washed with chloroform. The organic and aqueous layers were separated and the aqueous layer was further extracted with chloroform (2 x 100 mL). All organic phases were combined and dried with anhydrous sodium sulfate, followed by concentration under reduced pressure to give the crude 1-(2-chloropyridin-3-yl)ethanone as an oil. The crude product was purified by column chromatography to afford the pure 1-(2-chloropyridin-3-yl)ethanone (8 g, 81% yield).
* 1H NMR (CDCl3) δ 8.44 (dd, J = 5 and 2 Hz, 1H), 7.91 (dd, J = 7.5 and 2 Hz, 1H), 7.34 (dd, J = 7.5 and 5 Hz, 1H), 2.68 (s, 3H).
References
[1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1990, # 9, p. 2409 - 2415
[2] Patent: US2006/47126, 2006, A1. Location in patent: Page/Page column 30
[3] Patent: WO2011/5759, 2011, A2. Location in patent: Page/Page column 77
[4] Patent: WO2011/84486, 2011, A1. Location in patent: Page/Page column 106; 110-111
[5] Patent: US2013/296302, 2013, A1. Location in patent: Paragraph 0494
