Hydrochloric Acid → 4-Ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid

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Reaction Conditions

Reaction Steps

At room temperature, 2.75 N HCl (7.7 L) was added to a solution of crude ethyl 4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylate (1.1 kg) in EtOH (3.85 L). The mixture was heated for 10 hrs to 60-64° C. Next, the mixture was cooled to 50-54° C. and methanol was removed by vacuum distillation. The mixture was cooled to 20-25° C. and the pH was adjusted to 8.0 to 8.5 by addition of 30% sodium carbonate solution (8.5 L). The phases were separated and the aqueous layer was washed three times with DCM (4 L). Next, charcoal (0.7 kg) was charged to the aqueous layer and the layer was filtered through a celite bed. To the filtrate was added 1.5 N HCl until the pH had reached 2.0. The resulted slurry was stirred for 20 min at room temperature. The solids were filtered off, washed with water (15 L) and dried under vacuum at 50-55° C. until the loss on drying was less than 5 wt %. The crude product was suspended in ethyl acetate (5 L) and slurried for 15 min at 40° C. After cooling to room temperature, the solids were filtered off, washed with ethyl acetate (1 L) and dried at 40-45° C. under vacuum for 10 hrs to yield 4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid (0.76 kg; 58% yield for Steps 6 and 7).

Provenance & Evidence