Developing Efficient Nucleophilic Fluorination Methods and Application to Substituted Picolinate Esters

This report describes nucleophilic fluorination of 3 and 5-substituted picolinate ester substrates using potassium fluoride in combination with additive promoters. Agents such as tributylmethylammonium or tetraphenylphosphonium chloride were among the best additives investigated giving improved fluorination yields. Additionally, the choice of additive promoters could influence the potential formation of new impurities such as alkyl ester exchange. Other parameters explored in this study include additive stoichiometry, temperature influence on additive degradation, solvent selection, product isolation by solvent extraction, and demonstration of additive recycling.