Development of Practical and Scalable Synthetic Route for 1-(2,2,2-Trifluoroethyl)cyclopropane-1-carboxylic Acid

An efficient, scalable, and safe synthesis of 1-(2,2,2-trifluoroethyl)cyclopropane-1-carboxylic acid (compound 1) was developed, starting from the inexpensive and readily available trifluoro-iodopropane 18. This was accomplished through detailed optimization of the conditions for the key Simmons–Smith cyclopropanation reaction. The optimized process was used to prepare multi-kilograms of this intermediate, supporting early development activities of a pharmaceutical candidate.