Hydrochloric Acid → 1-(Tetrahydro-pyran-4-carbonyl)-piperidine-3-carboxylic acid (5-tert-butyl-isoxazol-3-yl)-amide

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Reaction Steps

To a solution of tetrahydro-pyran-4-carboxylic acid (54.66 mg; 0.42 mmol) and 1-hydroxybenzotriazole hydrate (56.76 mg; 0.42 mmol) in anhydrous DMF (1.5 mL) is added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (80.52 mg; 0.42 mmol) and the reaction mixture is stirred at room temperature for 15 minutes. After this time, piperidine-3-carboxylic acid (5-tert-butyl-isoxazol-3-yl)-amide; hydrochloride (90 mg; 0.313 mmol), triethylamine (0.044 mL; 0.313 mmol) and 4-dimethylaminopyridine (4.1 mg; 0.034 mmol) are added. The reaction mixture is stirred at room temperature for 18 hours. The mixture is diluted with ethyl acetate and then washed with water, saturated NaHCO3 aqueous solution then brine, dried over Na2SO4, filtered and concentrated in vacuo. Purification by flash chromatography on silica using methanol/methylene chloride then recrystallization from hot ethyl acetate provides the title compound, m/z 364 [M+H+].

Provenance & Evidence