A 25-mL RB-flask was charged with 5-(2-methoxyphenyl)pentanoic acid (53.0 mg, 0.250 mmol), tert-butyl-4-(3-amino-4-fluorophenyl)-1-piperidinecarboxylate (59.0 mg, 0.200 mmol), 1-[3-(Dimethylamino)propyl]-3-ethylcarbodimide hydrochloride (0.400 mmol, 62.0 mg), 4-dimethylaminopyridine (10 mg) in DMF:DCM (0.2:2.0 mL) at room temperature. The reaction mixture was stirred for 12 h and water (10.0 mL) was added to the reaction mixture. The organic layer was separated and the aqueous layer was extracted with CHCl3 (3×10 mL) The combined organic extracts were washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The crude residue was purified by chromatography (silica gel, hexanes:EtOAc 6:1) to afford tert-butyl 4-(4-fluoro-3-{[5-(2-methoxyphenyl)pentanoyl]amino}phenyl)-1-piperidinecarboxylate (48.4 mg, 50.0%): 1H NMR (400 MHz, CDCl3) δ 8.36-8.13 (m, 1H), 7.39 (s, 1H), 7.26-7.06 (m, 2H), 7.06-6.92 (m, 1H), 6.92-6.75 (m, 3H), 4.41-4.02 (m, 2H), 3.80 (s, 3H), 2.90-2.70 (m, 2H), 2.70-2.63 (m, 2H), 2.63-2.51 (m, 1H), 2.49-2.32 (m, 2H), 1.87-1.72 (m, 4H), 1.72-1.63 (m, 2H), 1.63-1.52 (m, 2H), 1.48 (s, 9H).
