Hydrochloric Acid → Ethyl 6-oxo-2-(trifluoromethyl)-1,4,5,6-tetrahydropyridine-3-carboxylate

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Reaction Steps

To 3-amino-4,4,4-trifluoro-2-butenoic acid ethyl ester (529 mL, 3.47 mol) was added acryloylchloride (600 mL, 6.95 mol) dropwise over a period of 15 min. The suspension was stirred at RT for 1 h. The temperature was slowly raised with stirring to 80° C. (HCl gas evolution) and maintained at 80° C. for 5 h. Stirring continued overnight at 40° C. The mixture was cooled, diluted with toluene (2 L) and n-heptane (2 L) to precipitate the product and stirred for another 15 min at room temperature. The product was isoloated by filtration, the filter cake was washed with toluene/n-heptane (1:2; 4×100 mL) and dried in vacuo at 40° C. for 5 h. This procedure yielded the title compound (286 g, 35%) as a white solid, MS (ISP) 236.1 (M−H)−. Concentration of the mother liquor and addition of toluene/n-heptane (1:10) yielded a second crop of 29.8 g.

Provenance & Evidence