Salt 39 (0.25 g, 0.58 mmol) was partitioned between IPAC (2.5 mL) and 5 wt % aqueous solution of K3PO4 (2.5 mL), and washed twice with 5 wt % aqueous K3PO4. The organic layer was washed with brine, dried over Na2SO4 and concentrated to give a crude 40. Crude 40 was dissolved in MeCN (1.75 mL) and H2O (1.0 mL). To this was added acid 14 (0.17 g, 0.53 mmol), HOBT (0.11 g, 0.70 mmol) and EDC.HCl (0.17 g, 0.87 mmol). The heterogeneous mixture was aged at 20-25° C. for 16 h. The homogeneous reaction was partitioned between IPAC and saturated aqueous NaHCO3, and washed twice with saturated aqueous NaHCO3. The organic layer was washed with 15 wt % aqueous citric acid solution, saturated aqueous NaHCO3 and brine. The organic layer was dried over Na2SO4 and concentrated to give product 41 (0.29 g, 89% yield). 1H NMR (400 MHz, CD3OD): δ 8.88 (d, J=1.9 Hz, 1H), 8.15 (d, J=1.9 Hz, 1H), 8.08 (dd, J=5.3, 1.6 Hz, 1H), 7.35 (dd, J=7.4, 1.6 Hz, 1H), 7.15-7.18 (m, 4H), 6.95 (dd, J=7.4, 5.3 Hz, 1H), 4.59 (dd, J=11.5, 7.0 Hz, 1H), 3.89-3.92 (m, 1H), 3.81 (dt, J=13.4, 3.2 Hz, 1H), 3.61-3.63 (m, 4H), 3.31-3.32 (m, 2H), 2.93-2.95 (m, 1H), 2.40 (s, 3H), 2.14-2.17 (m, 1H); 1.14 (d, J=6.5 Hz, 3H); 1H NMR (500 MHz, CDCl3): δ 8.91 (s, 1H), 8.56 (s, 1H), 8.17 (dd, J=5.0, 1.5 Hz, 1H), 8.05 (s, 1H), 7.30 (d, J=5.0 Hz, 1H), 7.20 (m, 3H), 7.12 (m, 2H), 6.89 (dd, J=7.5, 5.0 Hz, 1H), 5.00-4.94 (m, 1H), 4.55 (m, 1H), 3.93-3.90 (m, 1H), 3.81-3.76 (m, 2H), 3.68 (d, J=16.5 Hz, 1H), 3.31-3.23 (m, 2H), 3.17 (d, J=16.5 Hz, 1H), 2.75-2.67 (m, 2H), 2.41 (s, 3H), 1.11 (d, J=6.5 Hz, 3H); 13C NMR (100 MHz, CD3OD): δ 182.8, 171.8, 168.0, 166.7, 157.5, 148.7, 148.2, 139.5, 137.5, 136.8, 133.4, 132.0, 131.6, 130.8, 130.6, 128.4, 128.3, 127.4, 126.6 (q, J=283 Hz), 119.9, 58.1, 53.7, 53.0, 46.7 (q, J=33.4 Hz), 45.2, 42.1, 40.2, 28.8, 19.0, 13.6; HRMS: m/z=564.2219 (M+1), calculated m/z=564.2234 for C30H28F3N5O3.
