Logistic flexibility in the preparation of isomeric halopyridinecarboxylic acids

Although there are many conceivable ways to funtionalize, and specifically carboxylate, 2-chloro-4-(trifluoromethyl)pyridine optionally at all three vacant positions, it is more straightforward to prepare only the 2-chloro-4-(trifluoromethyl)pyridine-3-carboxylic acid (1) from this precursor and the other 6-chloro-4-(trifluoromethyl)pyridine-2- and -3-carboxylic acids (2 and 3) from a different one, viz. 5-bromo-2-chloro-4-(trifluoromethyl)pyridine. In the same manner, it proved more convenient to convert 5-chloro-2-(trifluoromethyl)pyridine in only two of the corresponding acids (6 and 7) and to make the third one (8) from 3-bromo-5-chloro-2-(trifluoromethyl)pyridine as an alternative starting material. All model substrates for functionalization were readily accessible from the correspondingly substituted chloroiodopyridine through heavy halogen displacement by in situ generated (trifluoromethyl)copper.