Tautomeric Shift Analysis Between Hydroxypyridine and Pyridone Forms Under Basic Reaction Conditions
The equilibrium between the hydroxypyridine and 5-fluoro-1H-pyridin-2-one forms dictates reaction kinetics and overall chemoselectivity. Under basic conditions, deprotonation occurs preferentially at the hydroxyl group, generating a resonance-stabilized enolate that favors O-alkylation. The fluorine substituent at the 5-position exerts a strong inductive effect, lowering the pKa and accelerating the shift toward the reactive pyridone tautomer. Process development teams must monitor this equilibrium closely, as temperature fluctuations during base addition can temporarily favor the less reactive hydroxypyrid
