Reaction Steps
A solution of 36I (0.371 g, 0.495 mmol) in acetonitrile (5 mL) and dichloromethane (5 mL) was cooled to 0° C. To this solution, was added phosgene (20% in toluene, 0.257 mL, 0.520 mmol). The mixture was stirred at 0° C. for 15 min, then bubbled with Ar for 25 min to remove excess phosgene and HCl. The resulting solution was added dropwise over 5 h via a syringe pump into a solution of TEA (0.690 mL, 4.95 mmol) in dichloromethane (200 mL). The solution was stirred for an additional 30 min and then concentrated. The crude product was purified by flash chromatography (1-15% MeOH/dichloromethane) to give di-Boc protected intermediate (0.326 g, 85%) as a diastereomeric mixture. The diastereomers were separated by a prep chiral HPLC (CHIRALCEL® OD 10 um 4.6×250 mm) to yield 36J (0.141 g, 0.182 mmol, 73.5% yield) as a yellowish solid. MS (ESI) m/z: 775.3 [M+1]+. 1H NMR: (400 MHz, CD3OD) δ ppm 8.05 (1H, d, J=5.81 Hz), 7.68 (1H, dd, J=7.83, 1.77 Hz), 7.61 (1H, d, J=9.09 Hz), 7.52 (1H, d, J=5.81 Hz), 7.46 (1H, d, J=8.08 Hz), 7.27 (1H, dd, J=9.22, 2.15 Hz), 7.18-7.24 (2H, m), 6.88 (1H, d, J=2.02 Hz), 6.71 (1H, dd, J=8.08, 2.27 Hz), 6.11 (1H, d, J=2.02 Hz), 5.73 (1H, s), 5.67 (1H, d, J=16.93 Hz), 4.65 (1H, t, J=10.99 Hz), 4.14 (1H, d, J=16.93 Hz), 3.96 (1H, dd, J=10.86, 4.29 Hz), 3.40 (3H, s), 2.31 (3H, s), 1.27 (25H, s).
