IMPROVED SYNTHESIS OF 2-(1-ADAMANTYL)-4-BROMOPHENOL AND 2-(1-ADAMANTYL)-4-BROMOANISOLE, INTERMEDIATES IN ADAPALENE SYNTHESIS

摘要

A new simple and environmentally friendly synthetic method for 2-(1-adamantyl)-4-bromophenol that did not use catalysts and solvents was developed. A new simplified preparation method for 2-(1-adamantyl)-4-bro-moanisole in one step instead of two was proposed. Both compounds are intermediates in the first and second synthetic steps to 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid (adapalene). Several synthetic approaches to the adamantyl derivatives of halophenols 2-(1-adamantyl)-4-bromophenol (I) and 2-(1-adamantyl)-4-bromoanisole (II) are known. These are intermediates in the synthesis of 6-[3-(1-adamantyl)-4-me-thoxyphenyl]-2-naphthoic acid (adapalene), a drug substance belonging to the atypical synthetic retinoid class that is used in dermatological practice as an effective agent against acneiform rash [1-3]. A method for preparing adapalene was described in patents [4, 5] and an article [1].