Hydrochloric Acid → 2-Methyl-2-{3-[1-(4-trifluoromethyl-benzylcarbamoyl)-piperidin-3-yl]-phenoxy}-propionic acid benzyl ester

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Reaction Steps

To a solution of 4-trifluoromethylbenzyl amine (170 mL, 1.19 mmol) in 5 mL toluene was added 1,1′-carbonyldiimidazole (193 mg, 1.19 mmol). This solution was stirred 18 h at ambient temperature. 2-methyl-2-(3-piperidin-3-yl-phenoxy)-propionic acid benzyl ester (Preparation 2, Method C; 421 mg, 1.19 mmol) was added in 5 mL toluene and the resultant solution was stirred 18 h at ambient temperature. The reaction was diluted with water (100 mL), acidified with 1N aqueous hydrochloric acid and extracted with ethyl acetate (2×50 mL). The organic extracts were combined, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resultant oil was flash chromatographed with 35% ethyl acetate/hexanes to yield 473 mg (72%) of the desired 2-methyl-2-{3-[1-(4-trifluoromethyl-benzylcarbamoyl)-piperidin-3-yl]-phenoxy}-propionic acid benzyl ester as a clear oil.

Provenance & Evidence