Reaction Steps
A solution of 29A (133 mg, 0.161 mmol) in acetonitrile (3 mL) and dichloromethane (6 mL) was cooled to 0° C. To this solution was added phosgene (20% in toluene, 0.088 mL, 0.178 mmol). The mixture was stirred at 0° C. for 5 min, and rt for 1 h. The mixture was 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 (0.225 mL, 1.614 mmol) in CH2Cl2 (260 mL). The solution was stirred for 16 h, concentrated and purified by flash chromatography to give a mixture of diastereoisomers (96 mg, 0.113 mmol, 70.0% yield). The diastereoisomers were separated by a prep chiral HPLC equipped with a IA column to give 29B (44 mg, 0.052 mmol, 46.3% yield). MS (ESI) m/z: 850.2 [M+1]+. 1H NMR (500 MHz, methanol-d4) δ ppm 8.09 (1H, d, J=5.8 Hz), 7.77 (1H, d, J=7.7 Hz), 7.53 (1H, d, J=6.1 Hz), 7.50 (1H, d, J=8.0 Hz), 7.42 (1H, d, J=11.8 Hz), 7.00-7.09 (2H, m), 6.61 (2H, dd, J=12.1, 1.9 Hz), 6.24 (1H, s), 5.76 (1H, d, J=17.9 Hz), 5.72 (1H, t, J=2.9 Hz), 4.62 (1H, t, J=11.1 Hz), 4.21 (1H, d, J=17.9 Hz), 3.96 (1H, dd, J=10.6, 4.3 Hz), 3.47 (1H, ddd, J=11.4, 7.0, 4.4 Hz), 3.32-3.38 (3H, m), 2.97 (1H, dd, J=4.8, 3.2 Hz), 2.22-2.33 (3H, m), 1.25-1.37 (24H, m), 1.03-1.13 (2H, m).
