In a flask (3R,4R)-4-benzyloxycarbonylamino-piperidine-1,3-dicarboxylic acid 1-tert-butyl ester (3.93 g, 10.4 mmol) was dissolved in dichloromethane (200 mL) and then benzotriazol-1-yloxy-tripyrrolidinophosphonium hexafluorophosphate (6.48 g, 12.5 mmol) and triethylamine (3.3 mL, 23.7 mmol) were added. After stirring for 5 minutes, (S)-3-(4-fluorobenzyl)-piperidine (2.21 g, 11.4 mmol) was added. The mixture was stirred for 16 hours. The reaction mixture was extracted with water (50 mL) and brine (50 mL). The organic layer was dried with magnesium sulfate, filtered, and concentrated in vacuo to give a crude orange glass (10.49 g). Purification by flash column chromatography (50-70% ethyl acetate/hexanes) provided a colorless oil (4.79 g, 83%). 1H NMR (300 MHz, CDCl3), δ: 7.32 (m, 2H), 7.26 (m, 3H), 7.07 (m, 2H), 6.95 (m, 2H), 5.04 (m, 2H), 4.41 (d, 1H, J=13), 4.12 (bm, 2H), 3.83 (bm, 2H), 3.06 (bm, 1H), 2.76 (bs, 2H), 2.60 (dd, 2H, J=14, J′=6), 2.37 (m, 2H), 1.90 (bs, 1H), 1.63 (bm, 2H), 1.45 (m, 9H), 1.12 (m, 3H), 0.87 (m, 1H).
