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

Participants

Reaction Conditions

Reaction Steps

Methyl 3-oxo-3-(3-(trifluoromethyl)phenylamino)propanoate (39.5 kg, 1 mol eq, limiting reagent) was dissolved in ethanol (197.5 L, 5.0 rel vol). Sodium methoxide solution in methanol (74.6 kg, 25% w/w, 2.3 mol eq) was charged followed by an ethanol line wash (11.9 L, 0.3 rel vol). trans-4-Methoxy-3-buten-2-one (19.2 kg, 1.2 mol eq) in ethanol (26.5 L, 0.67 rel vol) was charged. The reaction was heated to 65° C. and stirred at this temperature until the reaction was deemed complete as judged by HPLC analysis. Water (67.2 L, 1.7 rel vol) and 2 M aqueous sodium hydroxide (29.6 L, 0.75 rel vol) were then added and the reaction mixture was stirred for 1 hour. To the solution was added 8 M aqueous hydrochloric acid (237.0 L, 6 rel vol) and the mixture stirred for a further 1 hour. The solution was cooled, stirred and isolated by filtration. The solid was washed with water (79.2 L, 2 rel vol) and iso-hexane (59.2 L, 1.5 rel vol) and dried to constant weight to yield the title compound (28.6 kg, 96.2 mol, 63% (uncorrected for assay)); 1H NMR (CDCl3): δ 2.14 (s, 3H); 6.57 (d, 1H, J=7.4 Hz); 7.46 (d, 1H, J=8.2 Hz); 7.52 (s, 1H); 7.77 (t, 1H, J=7.8 Hz); 7.85 (d, 1H, J=7.9 Hz); 8.53 (d, 1H, J 7.4 Hz); 13.66 (s, 1H) ppm; LCMS: m/z 298.3 (MH+).

Provenance & Evidence