A Practical Synthesis of Lithium 3-Fluoropyridine-2-carboxylate

Abstract

A practical and efficient method for the preparation of lithium 3-fluoropyridine-2-carboxylate as well as its four regioisomer is described. 3-Fluoropyridine can be regioselectively lithiated on C-2 or C-4 depending on the reaction conditions. A quench procedure with carbon dioxide was developed which conveniently provides the lithium carboxylate in high yield and purity.

Acknowledgments

The authors thank Ms. Jennifer Reavis and Dr. Jian Wang of the Department of Chemical Engineering R & D at Merck Research Laboratories for providing us with the carbon dioxide solubility data and solubility data on lithium 3-fluoropyridine-2-carboxylate.