Diisopropylethylamine → 1-[4-(4-Nitro-3-trifluoromethyl-phenylamino)-piperidin-1-yl]-3-[4-(4-trifluoromethyl-phenyl)-piperidin-1-yl]-propan-1-one

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Reaction Steps

3-[4-(4-Trifluoromethyl-phenyl)-piperidin-1-yl]-propionic acid lithium salt (118 mg; 0.38 mmol, prepared in accordance with Example 13), diisopropylethyl amine (137 μL; 0.76 mmol) and tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (145 mg; 0.38 mmol) are diluted in a 2 to 1 mixture of dimethylformamide and tetrahydrofuran (12 mL) and the resulting solution is stirred for 5 minutes. A solution of (4-nitro-3-trifluoromethyl-phenyl)-piperidin-4-yl-amine hydrochloride (114 mg; 0.35 mmol, prepared in accordance with Example 8) in dimethylformamide (4 mL) is added and the reaction is then stirred for 2 hours at room temperature. Following dilution with dichloromethane (50 mL), the organic layer is sequentially washed with water (15 mL), aq. sat. sodium hydrogen carbonate (15 mL), is dried over magnesium sulfate and concentrated under reduced pressure. The desired product is finally obtained in pure form (103 mg; 0.18 mmol) following purification by preparative HPLC. The structure was confirmed using Protocol II-A. Calculated mass=572; observed mass=573; HPLC retention time=3.62 min.

Provenance & Evidence