A mixture of N-(3-{1-[(3R)-3-hydroxy-3-phenylpropyl]-4-piperidinyl}phenyl)-2-methylpropanamide (9.53 mg, 0.0250 mmol), 2,5-difluorophenol (6.50 mg, 0.050 mmol), triphenylphosphine (9.80 mg, 0.0375 mmol) and diethyl azodicarboxylate (5.22 mg, 0.0300 mmol) in THF (1.0 mL) was stirred at room temperature for 3 days. Chromatography using silica preparative TLC plates [2.5% of NH3 (2.0 M in methanol) in CHCl3] gave the desired product (3.60 mg, 29.3% yield) as a thick oil: 1H NMR δ 7.46 (s, 1H), 7.40–7.32 (m, 4H), 7.31–7.20 (m, 2H) 7.17 (s, 1H), 7.01–6.92 (m, 2H), 6.65–6.42 (m, 2H), 5.27 (m, 1H), 3.13 (m, 2H), 2.64 (m, 2H), 2.51 (m, 2H), 2.28–1.80 (m, 8H), 1.25 (d, 6H, J=7.1 Hz); ESMS t/e: 493.4 (M+H)+.
