3-[[1-(tert-Butoxycarbonyl)-2(S)-azetidinyl]methoxy]-5-(trimethylstannyl)pyridine (214 mg, 0.50 mmol) and 3-(2-iodophenyl)-1-propanol (131 mg, 0.50 mmol) were dissolved in anhydrous DMF (2 mL) in a 10 mL round-bottom flask with a magnetic stirrer. CsF (152 mg, 1.0 mmol, 2.0 equiv.), CuI (9.5 mg, 50 μmol, 0.1 equiv.) and Pd(PPh3)4 (29 mg, 25 μmol, 0.05 equiv.) were added. The flask was equipped with a condenser, and the atmosphere was exchanged with N2 (3 times). The mixture was stirred in a 130° C. oil bath for 26 h and cooled to room temperature. The solvent was evaporated (oil pump, 60° C.), and the residue was purified by CC on silica gel (28×1.0 cm, EtOAc) to give the crude product as a yellow oil. This material was further purified by preparative HPLC in two portions (Supelco Discovery C18, 250×21.2 mm, 5 μm particle size, UV detection at 270 nm, flow rate 12.5 mL/min, gradient from 20% to 100% CH3CN in water within 40 min, then 100% CH3CN for 20 min; tR 23.4-24.5 min) to give, after evaporation, the product as a colorless glass (128 mg, 64%). [α]546−51.3; [α]589−43.3 (c 9.15 g/L, EtOAc). 1H NMR (CDCl3, 400 MHz) δ 8.34 (d, 1H, J=2.8 Hz), 8.19 (d, 1H, J=1.4 Hz), 7.37-7.32 (m, 2H), 7.29-7.23 (m, 2H), 7.20 (d, 1H, J=7.3 Hz), 4.56-4.49 (m, 1H), 4.40 (dd, 1H, J=10.0, 4.6 Hz), 4.61 (dd, 1H, J=10.1, 2.7 Hz), 3.90 (t, 2H, J=7.8 Hz), 3.55 (q, 2H, J=5.5 Hz), 2.70-2.64 (m, 2H), 2.42-2.28 (m, 2H), 1.80-1.71 (m, 2H), 1.39 (s, 9H).
