부산대학교 도서관

Allergic rhinitis (AR) is an important allergic inflammatory disease, affecting 30‐60 million people annually in the USA. The most important class of drug used in the treatment of AR is second‐generation H1‐antihistamines (highly selective and non‐sedating drugs) like levocetirizine, desloratadine and fexofenadine. Different synthetic strategies are reported for the preparation of fexofenadine hydrochloride, but these approaches involve the formation of byproducts, either toxic or difficult to remove. The aim of this work is to find a new, efficient and scalable synthetic approach for the preparation of fexofenadine hydrochloride. The final product was assembled from methyl 2‐(4‐bromophenyl)‐2‐methylpropanoate, 3‐butyn‐1‐ol and azacyclonol, cheap and commercially available raw materials. A key step allows to build the central oxygenated‐C4‐moiety through a key 5‐membered intermediate, avoiding toxic or expensive reagents and catalysts. The 8‐step synthesis is competitive with existing protocols, leading to fexofenadine hydrochloride in 59% overall yield. An alternative synthesis of fexofenadine starting from readily available and cheap starting materials was developed. The 8‐step synthesis allowed to obtain fexofenadine in 59% overall yield on a >100g scale and was easily adapted to the preparation of the cognate API terfenadine. [ABSTRACT FROM AUTHOR]