2,2,2-Trifluoroethanol → 5-Bromo-6-(2,2,2-trifluoro-ethoxy)-2-trifluoromethyl-nicotinic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

5-Bromo-1,6-dihydro-6-oxo-2-(trifluoromethyl)-3-pyridinecarboxylic acid ethyl ester (111 g, 0.35 mol) was dissolved in tetrahydrofuran (1600 mL). To the solution were added trifluoroethanol (38 mL, 0.53 mol), triphenylphosphine (117 g, 0.42 mol) and diisopropyl azodicarboxylate (89.4 mL, 0.42 mol) at 0° C. The mixture was stirred for 30 min at 0° C., for 1 h at room temperature and for 18 h at 50° C. The mixture was cooled, poured into n-heptane (3.8 L) and extracted with 80% methanol (2×3.8 L). The methanol phase was extracted with another 3.8 L of n-heptane, the n-heptane phases were combined and dried with MgSO4. The solvent was removed in vacuo to give the title compound (121.5 g) as yellowish oil.

Provenance & Evidence