CA3253169A1 — Process for preparing tapinarof

USPTO Abstract

There is a need for large-scale production of antibacterials, antioxidants and therapeutic compounds including anti-cancer compounds with low toxicity. The present invention provides processes for the preparation of 3, 5-Dihydroxy-4-isopropyl-trans-stilbene or a salt or solvate thereof and intermediates used therein. The processes comprise decarboxylation, esterification, cyclization, halogenation and aromatization. In some embodiments the 3, 5-Dihydroxy-4-isopropyl-trans-stilbene is prepared from (E)-2-chloro- 2-isopropyl-5-styrylcyclohexane-l,3-dione. Also disclosed are crystal forms of 3, 5- Dihydroxy-4-isopropyl-trans-stilbene or a salt or solvate thereof and pharmaceutical compositions comprising same. The compounds and processes of the present invention can be manufactured on a larger scale, including with high-yielding synthesis, and have low toxicity.