Reaction Steps
A solution of 1A (1.173 g, 1.538 mmol) in acetonitrile (8 mL), dichloromethane (8 mL) and DMPU (0.6 mL) was cooled to 0° C. To this solution was added phosgene (20% in toluene, 0.837 mL, 1.692 mmol). The mixture was stirred at 0° C. for 15 min. and then bubbled with Ar for 10 min to remove excess phosgene. The resulting solution was added dropwise over 3 h (via a syringe pump) into a solution of TEA (2.144 mL, 15.38 mmol) in dichloromethane (400 mL) at 40° C. The yellow solution was stirred for an additional 30 min. Reaction mixture was concentrated, suspended in EtOAc (250 mL), washed with water (2×200 mL), brine (1×100 ml) and dried (Na2SO4). EtOAc was removed under reduced pressure and the residue was purified by Isco: (40 g) 50-100% EtOAc/hexanes. Fractions were combined and concentrated under reduced pressure to give product as a mixture of diastereomers. The diastereoisomers were separated by chiral HPLC (Chiral OD 10 um 4.6×250 mm; sol. A heptane; sol. B 50% MeOH-50% EtOH) to give 1B (0.200 g, 0.254 mmol, 33.0% yield): MS (ESI) m/z: 788.1 [M+1]+; Purity 95%; 1H NMR: (400 MHz, CD3OD) δ ppm 8.04 (1H, d, J=5.50 Hz), 7.68 (1H, d, J=6.05 Hz), 7.60 (1H, d, J=9.34 Hz), 7.51 (1H, d, J=6.05 Hz), 7.46 (1H, d, J=7.70 Hz), 7.40 (1H, d, J=8.24 Hz), 7.27 (1H, dd, J=8.79, 2.20 Hz), 7.22 (1H, s), 6.87 (1H, d, J=2.20 Hz), 6.63 (1H, dd, J=8.52, 2.47 Hz), 5.99 (1H, d, J=2.20 Hz), 5.71 (1H, s), 5.35 (1H, d, J=17.04 Hz), 4.65 (1H, t, J=11.27 Hz), 3.95 (1H, dd, J=10.99, 4.40 Hz), 3.65 (1H, s), 3.44-3.53 (1H, m), 3.34 (3H, s), 2.31 (3H, s), 1.31 (3H, d, J=7.15 Hz), 1.27 (18H, s).
