Adapalene synthesis

Yield:106685-40-9 99%

Reaction Conditions:

Stage #1: 3-(1-adamantyl)-4-methoxyphenylboronic acid;6-bromo-2-naphthoic acidwith potassium carbonate;palladium 10% on activated carbon in tetrahydrofuran;water; for 8 h;Heating / reflux;
Stage #2: with hydrogenchloride;water in tetrahydrofuran; for 1 h;Product distribution / selectivity;

Steps:

3

Example 3 :Preparation of 6- [3- (1-adamantyl) -4-methoxyphenyl] -2- naphthoic acid (I) :20 ml (12 vol) of tetrahydrofuran, 2 g (7 mmol) of 3-adamantyl-4-methoxyphenylboronic acid (II), 1.65 g (6.6 mmol) of 6 -broτno-2 -naphthoic acid (III) and 20 mL of a 2 M aqueous potassium carbonate solution are introduced into a round-bottomed flask equipped with EPO stirring and under a nitrogen stream. 0.7 g (5%) of 10% palladium on carbon (50% wet; Keraeus type K-0218) is then introduced.The medium is heated under reflux for 8 hours. The catalyst is filtered on a cartridge, and then slowly poured over 30 ml of a 1 N aqueous hydrochloric acid solution.The medium is kept stirring for one hour. The precipitate is filtered, washed with water and then dried under reduced pressure. 2.06 g of 6- [3- (1- adamantyl) -4-methoxyphenyl] -2-naphthoic acid are obtained in the form of a white solid whose purity, determined by HPLC, is 99.9% (yield = 79%; m.p. 321°C) .

References:

WO2006/108717,2006,A2 Location in patent:Page/Page column 11-12