An Efficient Method for the Synthesis of Adapalene as an Active Pharmaceutical Ingredient Using Zinc Nanoparticles

In this study, the synthesis of adapalene as an active pharmaceutical ingredient on a laboratory scale is examined. Our effort was focused on catalyzing C-C coupling as a difficult step in the adapalene total synthesis, using the zinc nanoparticles as well as eliminating the magnesium reagent. The use of zinc nanoparticles in C-C coupling is associated with increased yields compared with its bulk powder form. The best results were obtained using 1- (5-bromo-2-methoxy phenyl) adamantane and methyl 6-bromo-2-naphthoate in the presence of zinc nanoparticles in dry tetrahydrofuran followed by adding NiCl2 (DPPE) as the catalyst. Replacing the magnesium with zinc nanoparticles, this reaction can scale up to higher scales.