Development and Scale-Up of 7-COOH CBD Synthesis, a Key Cannabinoid Metabolite

This article describes the process development required for the manufacture of a cannabidiol (CBD) metabolite, 7-carboxy cannabidiol (7-COOH CBD), starting from ∼0.5 mT of CBD. A laboratory-scale synthetic route to 7-COOH CBD was not scalable, primarily due to the reliance on chromatography. The route was shortened from 9 to 7 steps by altering the protecting group strategy. Byproduct formation was a major hurdle toward developing a robust process as was identifying points of purification. Chromatography was circumvented, and purification was achieved through base washes, resin treatment, dicyclohexylamine (DCHA) salt formation, and methanol slurry at the final step. Overall, a scalable process was developed for the conversion of CBD to 7-COOH CBD, with pilot-scale manufacturing processing of 30 kg of CBD delivering 1.99 kg of 7-COOH CBD. Further scaling was carried out to deliver 31.79 kg of 7-COOH CBD starting from ∼0.5 mT of CBD.