2-Aminopyridine → 2-(chloromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one

Participants

Reaction Conditions

Reaction Steps

15 g (159.4 mmol) of 2-aminopyridine (10) was combined with approximately 80 g of polyphosphoric acid and heated to 120° C. to allow stirring. To the resulting solution was added slowly 30.5 mL (223.2 mmol) of ethyl-4-chloroacetoacetate and stirred at 120° C. under nitrogen for two hours. The hot reaction mixture was then poured over 1500 mL of ice water and stirred vigorously. The aqueous layer was separated and extracted with methylene chloride (6×, approximately 6 L). The combined organic layers were washed with saturated NaHCO3 and brine and dried over MgSO4 and activated carbon. The solvent was removed in vacuo yielding 30.7 g (157.7 mmol, 99%) of 2-(chloromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one (11) as a white solid.

Provenance & Evidence