Reaction Steps
Pd-black (70 mg) was added to a solution of 5 (1 g, 3.05 mmol) in MeOH (27 mL) under N2. The resulting suspension was thoroughly degassed and H2 introduced. After 18 h the suspension was degassed, N2 introduced, filtered through celite (MeOH as eluant) and the solvent removed to give crude 5,5-bis(aminomethyl)-1-O-tert-butyldimethylsilyl-3-oxo-hexan-1-ol (6) (800 mg, 2.90 mmol). This was dissolved in dioxan: 1M aq. NaOH (2:1, 20 mL) and the resulting solution cooled to 0° C. Boc2O (1.4 g, 6.41 mmol) was added and after 30 min. the resulting mixture warmed to RT. After 3 h the reaction mixture was acidified to pH 4 with 1M KHSO4 (aq.) and partitioned between EtOAc (300 mL) and water (100 mL). The aqueous layer was further extracted with EtOAc (200 mL). The organic fractions were combined, washed with sat. NaHCO3 (aq., 100 mL), brine (100 mL), dried (MgSO4), filtered and the solvent removed. The residue was purified by flash chromatography (EtOAc: hexane, 1:9 to 1:3) to give 5,5-bis(aminomethyl)-1-O-tert-butyldimethylsilyl-N,N-di-tert-butoxycarbonyl-3-oxo-hexan-1-ol(7). (1.04 g, 72% over 2 steps) as a colorless oil; IR (film) 3360 (NH), 1701, (amide I), 1508 (amide II) cm−1; 1H NMR (CDCl3, 400 MHz) δ-0.02 (s, 6H, Si(CH3)2), 0.75 (s, 3H, H-6), Q. 81 (s, 9H, SiC(CH3)3), 1.34 (s, 18H, OC(CH3)3×2), 2.83 (dd, 2H, JH,NH 5.3 Hz, JH,H′ 14.0 Hz, —CHH′N—×2), 3.00 (dd, 2H, JH′,NH 7.9 Hz, JH,H′ 14.1 Hz, —CHH′N—×2), 3.16 (s, 2H, H-4), 3.39 (t, 2H, J 4.9 Hz, H-2), 3.65 (t, 2H, J 4.9 Hz, H-1), 5.30 (br t, 2H, J 6.8 Hz, NH×2); 13C NMR (CDCl3, 100 MHz) 8-5.4 (Si(CH3)2), 18.2 (SiC(CH3)), 18.8 (C-6), 25.7 (SiC(CH3)3), 28.3 (OC(CH3)3×2), 40.2 (C-5), 44.4 (—CH2N—), 62.3, 72.8, 76.3 (C-1, C-2, C-4), 78.7 (OC(CH3)3×2), 156.7 (—NH(CO)O—×2); MS m/z (FAB+): 351 (M+Na+, 3), 329 (M+H+, 45).
