N-bromobutanimide → Ethyl 5-bromo-6-hydroxy-2-(trifluoromethyl)nicotinate

Participants

Reaction Steps

To a solution of 1,6-dihydro-6-oxo-2-(trifluoromethyl)-3-pyridinecarboxylic acid ethyl ester (157.6 g, 0.60 mol) in tetrahydrofuran (1500 mL) was added with stirring N-bromosuccinimide (124.3 g, 0.66 mol). The mixture was stirred for 1 h at room temperature. Two thirds of the solvent were removed in vacuo and the remaining material was poured portionwise (15 min) with stirring into cold water (20 L). The product precipitated and the suspension was stirred for 1 h at room temperature, filtered and the filter cake was washed extensively with water (6×200 mL). The filter cake was redissolved in ethyl acetate (2000 mL), dried with MgSO4 and concentrated to a volume of ˜300 mL. This solution was added dropwise into n-heptane (800 mL) to precipitate the product. Filtration and washing with n-heptane/ethyl acetate (4:1, 4×50 mL) and drying (in vacuo, 40° C.) yielded the title compound (93 g) as a white solid. Concentration of the mother liquor and addition of n-heptane/ethyl acetate (3:1, 150 mL) yielded a second crop of 16.4 g.

Provenance & Evidence