Process development of 4-isopropyl-3,5-dimethoxybenzoic acid, the first intermediate of Tapinarof


Prió Targa, Miquel


Psoriasis is a disease caused by the immune system itself which mainly affects the skin and is mainly treated with topical therapies, in addition, this disease can have a comorbid effect, that is to say, the disease in question together with another are mutually aggravated. In my research, I will carry out the development of a synthesis stage of Tapinarof, a medicine for topical use aimed at the most widespread type of psoriasis: the plaques.
Tapinarof is a molecule that reduces the effects caused by psoriasis such as inflammation, oxidative stress, as well as increasing the skin's protective barrier. Due to the recent approval by the FDA of Tapinarof, a project by Ferrer was considered to obtain a more economical drug. In this project, the raw material for the synthesis of Tapinarof has been studied, specifically the formation of the first intermediate TPN1, starting initially from DIMBAC. The focus of the research is the study of the Friedel-Crafts alkylation reaction of DIMBAC to form TPN1. During this process, the different parameters have been studied and evaluated for optimization. After an exhaustive search it was possible to obtain a yield of 80% with a purity of 99.5%. Finally, to check the robustness of these results and the process, it has been extrapolated to a test of approximately 1Kg of DIMBAC. Despite obtaining slightly lower results than expected, we can affirm that the robustness of the process has been verified.



Marquillas Olóndriz, Francisco


IQS SE - Master’s Degree in Pharmaceutical Chemistry