A Scalable One-Pot Process for the Synthesis of Florfenicol Phosphodiester

A practical and scalable one-pot process for the preparation of florfenicol phosphodiester (3), a new water-soluble prodrug of florfenicol (1), has been developed by adopting the phosphorylating system of POCl3/pyridine/CH3CN. The yield of 3 was 80.72%, and its HPLC purity reached as high as 99.20%, while the content of the maximum impurity was reduced to 0.28% under the optimum conditions. The present process has proven to be reliable on 500-g and 4-kg scale in the pilot plant.