Hydrochloric Acid → 4-(Adamantan-1-ylmethoxy)-2-fluoro-5-methylbenzoic acid

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Reaction Steps

To a solution of 1-adamantane methanol (2.40 g, 14.40 mmol) in anhydrous dimethylsulfoxide (20 ml) was added potassium tert-butoxide (4.86 g, 43.30 mmol) and the suspension was stirred at ambient temperature for 30 min. 5-chloro-2,4-difluorobenzoic acid (2.50 g, 14.40 mmol) was added to the reaction mixture and stirred at 50° C. for 72 h. The reaction mixture was acidified to pH=1 with cold aqueous hydrochloric acid solution (1N), followed by addition of 25% aqueous ammonium chloride solution (200 mL). The solid was collected by filtration and washed with water and a mixture of hexanes/diethyl ether (3/1, v/v). Recrystallization of the crude product from ethyl acetate and hexanes to afford the title compound as a beige color solid (0.77 g, 17%): MS (ES+) m/z 437.2 (M+1).

Provenance & Evidence