Tributylstannane → HCID 11307964, compound

Participants

Reaction Steps

Crude (2S,3R)-1-tert-butoxycarbonyl-3-(3-hydroxypropyn-1-yl)-2-phenylpiperidin-3-ol (Description 18; 45 g) was dissolved in toluene (750 ml) and degassed with nitrogen. Tetrakis(triphenylphosphine) palladium (0) (2.30 g, 2.0 mmol) in toluene (600 ml) was added and the mixture was degassed. Tributyltin hydride (35.78 ml, 38.71 g, 133 mmol) was added dropwise over 15 minutes, with stirring and cooling (internal temperature below 25° C.). The mixture was stirred at room temperature for 1 hour, then the solvent was evaporated under reduced pressure. The residue was dissolved in tetrahydrofuran (600 ml) and triphenylphosphine (34.88 g, 133 mmol) was added. A solution of diethyl azodicarboxylate (20.94 ml, 23.16 g, 133 mmol) in tetrahydrofuran (150 ml) was added dropwise with stirring and cooling and the mixture was stirred at room temperature for 1 hour. The solvent was evaporated under reduced pressure, acetonitrile (600 ml) was added and the mixture was extracted with hexane (8×150 ml). The hexane fractions were combined and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with dichloromethane/ethyl acetate (100:0 increasing to 99:1) to give the title compound as a yellow oil (53.64 g, 67% from (2s,3S)-1-tert-butoxycarbonyl-3-hydroxy-2-phenylpiperidine). 1H NMR (CDCl3) δ 7.38-7.40 (2H, m), 7.15-7.25 (3H, m), 5.96 (1H, t, J 2.3 Hz), 4.93 (1H, s), 4.63 (1H, dd, J 2.23, 12.9 Hz), 4.22 (1H, dd, J 2.23, 12.9 Hz), 4.09-4.14 (1H, m), 3.09-3.17 (1H, m), 1.95-1.99 (1H, m), 1.83-1.86 (1H, m), 1.72-1.76 (2H, m), 1.40-1.51 (6H, m), 1.38 (9H, s), 1.25-1.32 (6H, m), and 0.86-0.99 (15H, m).

Provenance & Evidence