Reaction Steps
Formic acid (138 ml, 3.77 mmol) was added to a stirred, degassed solution of (2S,3R)-1-tert-butoxycarbonyl-3-(3-hydroxypropyn-1-yl)-2-phenylpiperidin-3-ol (Description 7, 473 mg, 1.43 mmol), palladium (II) acetate (33 mg, 0.14 mmol), trio-o-tolylphosphine (85 mg, 0.28 mmol), tributylamine (1.12 ml, 4.87 mmol) and 2-iodoanisole (446 ml, 3.44 mmol) in N,N-dimethylformamide (3 ml) at room temperature and the resulting mixture was heated at 70° C. for 5 h. The mixture was cooled, filtered, diluted with ethyl acetate (50 ml), washed with water (100 ml), hydrochloric acid (2M, 50 ml) and saturated aqueous sodium chloride (50 ml), dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was chromatographed on silica gel, eluting with hexane/ethyl acetate (60:40) to give the title compound as a yellow glass (220 mg, 35%). 1H NMR (360 MHz, CDCl3) δ7.41 (2H, d, J 7.6 Hz), 7.22-7.34 (4H, m), 7.12 (1H, dd, J 1.7, 7.4 Hz), 6.94 (1H, t, J 7.5 Hz), 6.89 (1H, d, J 8.2 Hz), 5.84 (1H, s), 5.00 (1H, s), 4.40 (1H, d, J 12.7 Hz), 4.15 (1H, dd, J 6.0, 13.1 Hz), 4.05 (1H, d, J 12.5 Hz), 3.86 (3H, s), 3.44 (1H, dt, J 5.6, 12.3 Hz), 2.04-2.18 (1H, m), 1.80-1.96 (3H, m), 1.28 (9H, s), and 1.64-1.84 (3H, m). m/z (ES+) 440 (M+1).
