One-pot synthesis of methyl 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthenoate

Abstract

The key stage at the constructing backbone of 6-[3(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid (Adapalene) molecule is the formation of a C–C bond between 3-(1-adamantyl)-4-methoxyphenyl and 2carbomethoxy-6-naphthyl fragments. Among the most effective modern methods of C–C bond formation is known the process of catalytic coupling according to the method of Suzuki–Miyaura [1]. To use this method, one of the coupled fragments should bear a boron-containing functional group. For introducing such a group the most widely used method is the transmetallation of preliminarily prepared Grignard reagents or lithium derivatives at the action of a boron compounds with halogen or alkoxy residue as a leaving group. An alternative method of introducing this functional group is catalytic coupling of boron-containing nucleophilic agent with electrophilic aryl substrate, which unlike the transmetallation reaction can be performed in one stage [2]. The main advantage of direct catalytic heterofunctionalization of aryl halides is its easy technological application. Conditions of this reaction differ only slightly from that of Suzuki–Miyaura cross-coupling reaction (the latter requires a stronger base), therefore it is possible to carry out these two processes without separation of the intermediate arylboric acid pinacol ester, that is, to arrange it as a one-pot synthesis [3, 4].