Water → Methyl 1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylate

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Reaction Steps

To a solution of methyl 2-oxo-2H-pyran-3-carboxylate (375 mg, 2.43 mmol) in dry N,N-dimethylformamide (DMF) under room temperature (rt) was added 4-fluoroaniline (0.23 mL, 2.44 mmol), and the reaction mixture was stirred for 6 hours. To the mixture was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 465 mg, 2.43 mmol) and 4-dimethylaminopyridine (DMAP, 75 mg, 0.61 mmol), and was stirred for additional 12 hours. Reaction mixture was dumped to water followed by ethyl acetate partition. Organic layers were combined, washed by 3N hydrochloric acid and water, and concentrated in vacuo to give crude methyl 1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylate. Crude methyl ester was saponificated by 10% sodium hydroxide solution (10 mL) in methanol (20 mL). Reaction mixture was heated at 65° C. for 3 hrs. Solid precipitated during acidic workup by 3N hydrochloric acid was collected by filter, washed by methanol (small amount), water and diethyl ether, dried to give an intermediate compound, 1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid.

Provenance & Evidence