72093-14-2

18368-76-8

74-88-4

72093-14-2

The general procedure for the synthesis of 2-chloro-3,6-dimethylpyridine from 2-chloro-3-methylpyridine and iodomethane was as follows: n-butyllithium (1.4 M, 35.0 mL, 49.0 mmol) was slowly added to a hexane solution (15.0 mL) of 2-dimethylaminoethanol (2.15 g, 24.1 mmol) at -50 °C and stirred for 30 min. The reaction mixture was cooled to -75 °C, then a hexane (15.0 mL) solution of 2-chloro-3-methylpyridine (1.02 g, 8.0 mmol) was slowly added, ensuring that the temperature was kept below -70 °C. After 1.5 h, a THF (60.0 mL) solution of iodomethane (2.0 mL, 32.1 mmol) was slowly added, while keeping the temperature at -70 °C below. Remove the cold bath and slowly warm the mixture to 0°C. The organic layer was separated by careful addition of water (60.0 mL) for quenching and the aqueous layer was extracted with ether. The organic phases were combined, washed sequentially with water and brine, dried over anhydrous magnesium sulfate and concentrated to give the crude product. The crude product was purified by silica gel column chromatography (25% ether/hexane as eluent) to afford the light yellow oily target compound 2-chloro-3,6-dimethylpyridine (0.674 g, 60% yield). The product was characterized by 1H NMR (300 MHz, CDCl3): δ 2.33 (s, 3H); 2.49 (s, 3H); 6.98 (d, 1H, J=7.5 Hz); 7.41 (d, 1H, J=7.5 Hz).