A Greener Synthesis of Glycerol Phenylbutyrate (“Ravicti”)

A laboratory experiment was developed to enable students to synthesize Ravicti, a drug used to treat Urea Cycle Disorders (UCDs). In response to legislation restricting the use of dichloromethane (DCM), otherwise known as methylene chloride, this synthesis uses cyclopentyl methyl ether (CPME) as a less hazardous, hydrophobic ether solvent. When implemented with students, they synthesized Ravicti in good yield and purity while discussing the adaptations to the traditional process together with the underlying reaction mechanisms. Students also determine relevant green metrics such as process mass intensity, which they use to quantify and explain the greenness of the conventional and adapted procedures.