Chemical Properties
off-white solid
Uses
2,6-Dichloro-4-methylpyridine is used in preparation of substituted phenoxymethyl benzoic acids and related products as modulators of Mas-related G-protein receptor X4.
Synthesis
General procedure for the synthesis of 2,6-dichloro-4-methylpyridine from 2-chloro-4-methylpyridine-N-oxide: 2-chloro-4-methylpyridine-N-oxide was added to a 50mL round-bottomed flask, and 20mL of phosphorus oxychloride (POCl3) was added slowly and dropwise. (Note: the reaction is exothermic and slow addition of N-oxide to POCl3 is required to avoid violent reaction.) Subsequently, an additional 10 mL of POCl3 was added to the reaction mixture and the reaction system was heated to 95°C and maintained for 5 hours. Upon completion of the reaction, the mixture was cooled to room temperature and volatiles were removed by distillation under reduced pressure. The residue was slowly poured into 150 mL of saturated sodium bicarbonate (NaHCO3) aqueous solution and extracted with ethyl acetate (EtOAc, 3 x 50 mL). The organic phases were combined, washed with 50 mL of saturated brine and dried over anhydrous magnesium sulfate (MgSO4). The solvent was removed by concentration under reduced pressure and the resulting brown solid was purified by fast column chromatography on silica gel (eluent: 0 to 7% ethyl acetate/hexane gradient) to afford 1.56 g of the target product 2,6-dichloro-4-methylpyridine in 43% yield.
References
[1] Patent: US2004/198736, 2004, A1. Location in patent: Page/Page column 76
[2] Patent: US2011/9390, 2011, A1. Location in patent: Page/Page column 19
[3] Patent: WO2015/26792, 2015, A1. Location in patent: Paragraph 1056
