Synthesis of Adapalene

A Practical synthesis of Adapalene was described.Adapalene was prepared from 4-bromophenol and 1-adamantanol by four steps in 71.1% overall yield.4-Bromophenol was alkylated by 1-adamantanol to form 2-(1-adamantyl)-4-bromophenol(4).The compound 4 then reacted with dimethyl sulfate to give(5).Compound 5 was condensed to 6-bromo-2-naphthoic acid methyl ester(6) to produce 6-(3-(1-adamantyl)-4-methoxyphenyl)-2-naphthoate(7).Saponification of compound 7 methanol and LiOH afforded Adapalene(1).