Efficient Synthesis of 2-(Trifluoromethyl)nicotinic Acid Derivatives from Simple Fluorinated Precursors

Novel routes to 2-trifluoromethyl-nicotinic acid derivatives have been developed involving synthesis of the pyridine ring. These pyridyl compounds serve as key intermediates in the manufacture of the recently discovered COMT inhibitor, 3-(5-(3,4-dihydroxy-5-nitrophenyl)-1,2,4-oxadiazol-3-yl)-2-(trifluoromethyl)pyridine 1-oxide.