Synthesis of a Benvitimod Impurity: (Z)-3,5-Dihydroxy-4-Isopropylstilbene

Abstract

(E)-3,5-dihydroxy-4-isopropylstilbene (Benvitimod), a new medicine for the treatment of psoriasis and eczema, belongs to the hydroxystilbene family. The synthesis leads to the E-isomer, (Z)-3,5-dihydroxy-4-isopropylstilbene being present as a major impurity in the preparation of Benvitimod. We describe a synthesis of the Benvitimod impurity: (Z)-3,5-dihydroxy-4-isopropylstilbene starting from 3,5-dihydroxybenzoic acid, through an isopropyl reaction, esterification and etherification, reduction, oxidation, Perkin condensation, decarboxylation and demethylation. The optimal reaction conditions were also determined.