Hydrochloric Acid → 6-Methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxylic acid

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Reaction Steps

Methyl 3-oxo-3-(3-(trifluoromethyl)phenylamino)propanoate (62.0 kg, 1 mol eq, limiting reagent) was charged followed by ethanol (310 L, 5 rel vol, 5.3 rel vol). 4,4-dimethoxybutan-2-one (37.6 kg, 1.2 mol eq) was charged followed by an ethanol line rinse (18.6 L, 0.3 rel vol) and the temperature adjusted to 50° C. Sodium methoxide (30% w/w in methanol) (141.0 kg, 3.3 mol eq) charged maintaining the temperature below 55° C. An ethanol line rinse (31.0 L, 0.5 rel vol) was applied. The reaction was stirred until complete as judged by HPLC. Water (105.4 L, 1.7 rel vol) and 29% aqueous sodium hydroxide solution (17.2 kg, 0.52 mol eq) were charged. The reaction was stirred for 60 minutes. Hydrochloric acid (30% w/w) was charged until pH 2 achieved and was then cooled. The product was isolated by filtration, washed five times with water (5×124 L, 5×2 rel vol) and dried under vacuum to constant weight yielding the title compound (50.9 kg, 171.4 mol, 73.5%).

Provenance & Evidence