Ethyl 2-chloroacetoacetate → Ethyl 8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylate

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Reaction Steps

170 g of 3-[(2,6-difluorobenzyl)oxy]pyridine-2-amine (Example 4A; 719 mmol, 1 equivalent) were initially charged in 3800 ml of ethanol, and 151 g of powdered molecular sieve 3 Å and 623 g of ethyl 2-chloroacetoacetate (3.6 mol, 5 equivalents) were added. The resulting reaction mixture was heated under reflux for 24 h and then filtered off through kieselguhr and concentrated under reduced pressure. After relatively long standing (48 h) at RT, a solid precipitated out. This solid was filtered off, three times suspended in a little isopropanol and in each case filtered off again and finally washed with diethyl ether. This gave 60.8 g (23.4% of theory) of the title compound. The combined mother liquor of the filtration steps was chromatographed on silica gel using cyclohexane/diethyl ether as mobile phase. This gave a further 46.5 g (18.2% of theory; total yield: 41.6% of theory) of the title compound.

Provenance & Evidence