A mixture of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-bromonaphthalene (50 mg, 0.11 mmol) in THF (1 ml) was introduced into a Schlenk tube and was heated until its complete dissolution. Next, NaH (4.5 mg, 60% dispersion in mineral oil, 0.11 mmol) was added under argon atmosphere and at room temperature, and the mixture was stirred for 10 minutes. The obtained mixture was cooled to −60° C. and t-BuLi (1.7 M in penthane, 0.22 mmol) was added, dropwise, during a period of 30 minutes. Next, and at the same temperature, a continuous mild flow of CO2 (anhydrous gas) was introduced in the reaction for 1 h. After bringing the reaction to room temperature during 30 minutes with continuous flow of CO2, the mixture was diluted with aq HCl (5 ml, 2 M) and was vigorously stirred for 10 minutes. The resulting mixture was extracted with CHCl3 (3×5 ml) and the joined organic phases were evaporated to dryness once dried with Na2SO4, giving the crude of Adapalene.
