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.

中文翻译：

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关键大麻素代谢物 7-COOH CBD 合成的开发和放大

本文描述了从 ∼0.5 mT CBD 开始制造大麻二酚 (CBD) 代谢物 7-羧基大麻二酚 (7-COOH CBD) 所需的工艺开发。 7-COOH CBD 的实验室规模合成路线无法扩展，主要是由于对色谱法的依赖。通过改变保护基策略，路线从 9 步缩短到 7 步。副产物的形成是开发稳健工艺的主要障碍，确定纯化点也是如此。绕过色谱法，并通过碱洗、树脂处理、二环己胺 (DCHA) 盐形成和最后一步的甲醇浆液实现纯化。总体而言，开发了一种将 CBD 转化为 7-COOH CBD 的可扩展工艺，其中 30 公斤 CBD 的中试规模生产加工可产生 1.99 公斤 7-COOH CBD。从~0.5 mT CBD 开始，进一步进行缩放以提供 31.79 kg 7-COOH CBD。