Development of Scalable Synthesis for 7-COOH CBD

This article is a technical report that details the process development for synthesizing 7-carboxy cannabidiol (7-COOH CBD), a significant metabolite of cannabidiol (CBD). The report outlines the challenges encountered during laboratory scale synthesis, primarily due to the reliance on chromatography, which was not suitable for scaling. The original process was modified to reduce the number of steps from nine to seven by changing the protecting group strategy. Key purification steps were highlighted, including the use of base washes, resin treatment, and the formation of dicyclohexylamine (DCHA) salts. The report explains the transition from laboratory scale to pilot scale, where 30 kg of CBD yielded 1.99 kg of 7-COOH CBD, and further scaling reached 31.79 kg. The development process involved critical evaluations of each synthesis step and modifications to improve yield and efficiency while overcoming impurities and challenges in reaction conditions.