8-Methylimidazo[1,2-a]pyridine

Synthesis

General procedure for the synthesis of 8-methyl-imidazo[1,2-A]pyridine from 2-amino-3-methylpyridine and 2-bromo-1,1-diethoxyethane: 2-amino-3-methylpyridine (10 g, 92.5 mmol) and 2-bromo-1,1-diethoxyethane (36.4 g, 185 mmol) were dissolved in ethanol (100 mL). Subsequently, 48% aqueous hydrogen bromide solution (9 mL) was slowly added dropwise to the reaction solution. The reaction system was heated to 90 °C and after 26 h of reaction, the completion of the reaction was confirmed by LC-MS and then cooled to room temperature. The reaction system was first distilled under reduced pressure to remove ethanol, followed by neutralization of excess hydrobromic acid in the reaction with excess saturated aqueous sodium bicarbonate solution (100 mL) and solid sodium bicarbonate (15 g). The remaining mixture was extracted with ethyl acetate (200 mL x 3). All organic phases were combined, washed sequentially with deionized water (100 mL) and saturated brine (100 mL) each, dried with anhydrous sodium sulfate, and the solvent was subsequently removed by rotary evaporation. Finally, the remaining mixture was purified by silica gel column chromatography (eluent: dichloromethane/methanol = 0-10%) to afford 8-methyl-imidazo[1,2-a]pyridine (12 g, 98% yield).

References

[1] Patent: CN106279160, 2017, A. Location in patent: Paragraph 0259; 0263; 0264; 0265
[2] Bulletin of the Chemical Society of Japan, 1999, vol. 72, # 6, p. 1327 - 1334