5-fluorocytosine

Intermediate

Summary

A key intermediate in the synthesis of Emtricitabine (FTC) is the nucleobase 5-fluorocytosine (5FC). Herein, we describe a new route to 5FC starting from inexpensive precursors. Our process eliminates the use of gaseous fluorine to install the fluorine in 5FC. Fluorination with molecular fluorine requires specialized equipment and requires significant safety features in the manufacturing plant. The route combines inexpensive guanidine carbonate and another acyclic precursor to access 5FC efficiently. Further efficiencies are achieved through telescoping reactions and use of inexpensive reagents. The process is still being optimized and we predict there is room for improvement to reduce the overall environmental impact. Telescoping the processes will reduce the PMI which currently ranges from 9 to 27.

5-fluorocytosine Report

5-fluorocytosine