N-tert-butyl-1-{3(S)-amino-2(R)-hydroxy-4-phenylbutyl}-4(R)-phenylpiperidine-2(S)-carboxamide {prepared by hydrogenolysis (5% Pd/C, 1 atmosphere, MeOH, 2 h) from 0.605 mg (0.108 mmol) of N-tert-butyl-1-{3(S)-(benzyloxycarbonylamino)-2(R)-hydroxy-4-phenylbutyl}-4(R)-phenylpiperidine-2(S)-carboxamide (see entry 1 of Table I)} was dissolved in DMF (1.6 mL). The lithium salt of N-{(2-pyridinylmethoxy)carbonyl}isoleucine (586 mg, 0.228 mmol), 1-hydroxybenzotriazole (32 mg, 0.237 mmol) and N-ethyl-N'-{3-(dimethylamino)propyl}carbodiimide (45.4 mg, 0,237 mmol) were added to the solution. The mixture was stirred at room temperature for 18 h. Thereafter, the reaction mixture was diluted with Et2O, washed with H2O, a saturated aqueous solution of NaHCO3 (2×) and brine, dried (MgSO4) and evaporated to dryness. The resulting yellow oil was purified by flash chromatography (SiO2, eluent: CHCl3, MeOH, 97.5:2.5 and then 95:5) to give the title compound as a white solid (58.7 mg). FAB mass spectrum, m/z: 672 (M+H)+.
