Trifluoroacetic acid → 4-(2,3-Dimethoxybenzoyl)piperidine

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Reaction Steps

4-(2,3-dimethoxybenzoyl)-1-piperidinecarboxylic acid, 1,1-dimethylethyl ester (7) (˜0.1128 mol) was cooled to 0° C., treated with trifluoroacetic acid (85 mL), and stirred at ambient temperature for 1 hour. Following concentration in vacuo, the material was dissolved in water (300 mL), washed with hexane (2×110 mL) and then treated with solid sodium hydroxide (18 g). The resulting aqueous solution was then extracted with methylene chloride (3×170 mL). The combined organic extracts were washed with brine (220 mL), dried (MgSO4) and concentrated in vacuo. The resulting residue was dissolved in ethanol (110 mL), cooled to 0° C., treated with anhydrous hydrogen chloride gas until acidic, diluted with ether (110 mL) and stirred for 1 hour. The resulting solid was collected by filtration, then washed with a mixture of ethanol and ether (1:1, 110 mL) to afford 4-(2,3-dimethoxybenzoyl)piperidine (16) hydrochloride salt as a white solid (19.18 g, 53%).

Provenance & Evidence