Reaction Steps
NaBH3CN (0.94 g, 15 mmol) was added portionwise to a solution of 24 (1.46 g, 5 mmol) in acetic acid (40 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 NaHCO3 and extracted with EtOAc. The combined organic phases were washed with brine, dried and evaporated to give crude 4-(1,3-diacetoxypropan-2-yloxy)indoline (1.47 g, 100%) as a viscous oil: 1H NMR (90 MHz) δ 6.95 (t, J=7.2 Hz 1H), 6.24-6.68 (m, 2H), 4.62 (quintet, J=5.4 Hz, 1H), 4.20-4.46 (m, 4H), 3.64 (s, 1H), 4.52 (t, J=7.2 Hz, 2H), 2.94 (t, J=7.2 Hz, 2H), 2.06 (s, 6H). Without further purification, this material was dissolved in dry MeCN (40 mL) and treated with 4-azidobutyric acid (0.78 g, 6 mmol), followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.34 g, 7 mmol) and the mixture was stirred at room temperature overnight. The solvent was evaporated and the residue was taken up in EtOAc (50 mL) washed with dilute aq. HCl, saturated aq. NaHCO3 and brine, dried and evaporated. Flash chromatography [EtOAc-hexanes (2:3)] gave 25 (1.33 g, 64%) as white crystals, mp 61-63° C. (Et2O-hexanes); 1H NMR (500 MHz) δ 7.87 (d, J=8.2 Hz, 1H), 7.16 (t, J=8.2 Hz, 1H), 6.68 (d, J=8.2 Hz, 1H), 4.70 (quintet, J=5.3 Hz, 1H), 4.34 (dd, J=11.9, 5.7 Hz, 2H), 4.29 (dd, J=11.9, 4.8 Hz, 2H), 4.07 (t, J=8.5 Hz, 2H), 3.45 (t, J=6.4 Hz, 2H), 3.12 (t, J=8.4 Hz, 2H), 2.51 (t, J=6.9 Hz, 2H), 2.06 (s, 6H), 2.03 (quintet, J=6.6 Hz, 2H). Anal. Calcd for C19H24N4O6: C, 56.43; H, 5.98; N, 13.85. Found: C, 56.23; H, 5.98; N, 13.61.
