Reaction Steps
1-[4-(N-Phthalimido)butanoyl]-4-[1,3-bis(t-butyldimethylsilyloxy)propan-2-yloxy]indoline (15) and related compounds. NaBH3CN (1.79 g, 28.5 mmol) was added portionwise to a solution of the indole 14 (4.13 g, 9.5 mmol) in acetic acid (90 mL) and the mixture was stirred at room temperature for 1 h. The solvent was evaporated and the residue was diluted with water, neutralised with solid NaHCO3 and extracted with EtOAc. The combined organic phases were washed with brine, dried and evaporated to give 4-[1,3-bis(t-butyldimethylsilyloxy)propan-2-yloxy]indoline (3.14 g, 75%) as a viscous oil: 1H NMR (90 MHz) δ 6.82 (t, J=7.2 Hz 1H), 6.04-6.32 (m, 2H), 4.16-4.32 (m, 1H), 3.64-3.88 (m, 4H), 3.46 (t, J=7.2 Hz, 2H), 2.88 (t, J=7.2 Hz, 2H), 2.04 (s, 1H), 0.88 (s, 18H), 0.04 (s, 12H). This material was dissolved in dry MeCN (95 mL) and treated with 4-(N-phthalimido)butanoic acid (2.66 g, 11.4 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (2.55 g, 13.3 mmol) and the mixture was stirred at room temperature overnight. The solvent was evaporated and the residue was taken up in EtOAc, washed with 0.5 M aq. HCl, aq. NaHCO3 and brine, dried and evaporated. Flash chromatography [EtOAc-hexanes (1:4)→(2:3)→(1:1)] gave four products. The first eluted material was 15 (1.69 g) as white crystals, mp 118-120° C. (MeOH). This material was estimated by 1H NMR to contain ˜20% of 1-[4-(N-phthalimido)butanoyl]-4-[1-(t-butyldimethylsilyloxy)propan-2-yloxy]indoline 16. The second eluted material was 1-[4-(N-phthalimido)butanoyl]-4-[1-(t-butyldimethylsilyloxy)propan-2-yloxy]indoline 16 (0.22 g, 6%) as white crystals, mp 118-120° C. (Et2O-hexanes): 1H NMR (500 MHz) δ 7.81 (dd, J=5.4, 2.9 Hz, 2H), 7.71 (d, J=8.2 Hz, 1H), 7.68 (dd, J=5.4, 2.9 Hz, 2H), 7.07 (t, J=8.2 Hz, 1H), 6.51 (d, J=8.2 Hz, 1H), 4.13-4.19 (m, 1H), 4.02 (t, J=8.5 Hz, 2H), 3.74-3.92 (m, 6H), 3.10 (t, J=8.5 Hz, 2H), 2.47 (t, J=7.1 Hz, 2H), 2.15 (quintet, J=7.1 Hz, 2H), 1.23 (d, J=6.2 Hz, 3H), 0.90 (s, 9H), 0.10 (s, 3H), 0.08 (s, 3H). LRMS (ES+); calcd for (C29H38N2O5Si+H)+, 523; found, 523.4. Anal. Calcd for C29H38N2O5Si+H2O: C, 64.64; H, 7.45; N, 5.18. Found: C, 64.70; H, 7.13; N, 5.12.
