An Expedient Undergraduate Synthesis of Glycerol Phenylbutyrate, One of the Most Expensive Medications in the United States

The urea cycle disorder drug glycerol phenylbutyrate (Ravicti) is presently one of the most expensive medications in the United States, with annual costs estimated at $800,000 as of 2023. An expedient synthesis of this orphan drug was successfully adapted for the undergraduate organic chemistry laboratory. Activation of 4-phenylbutyric acid with thionyl chloride cleanly affords 4-phenylbutyryl chloride, which is then esterified with glycerol in the presence of N-methylimidazole. Glycerol phenylbutyrate is obtained in high yield and purity following silica gel column chromatography. It is anticipated that this synthesis can be readily implemented in other undergraduate organic chemistry laboratory programs, fostering student interest and engagement by highlighting the relevance of chemistry to the societal issue of drug pricing.