Reaction Steps
To a 4 mL vial were added N-((3S,7R,8R,9S)-8-(cyclopropylmethoxy)-7-(4-methoxybenzyl)-9-methyl-2-oxooxonan-3-yl)-3-hydroxy-4-methoxypicolinamide (85 mg, 0.166 mmol), CH2Cl2 (1 mL) and NEt3 (0.069 mL, 0.497 mmol), 3-methoxypropanoyl chloride (30.5 mg, 0.249 mmol), and DMAP (3 mg, 0.02 mmol), and the resulting light yellow solution was stirred at room temperature overnight. The reaction mixture was concentrated and purified by column chromatography on SiO2 (0→100% EtOAc/hexanes) to provide the title compound as a colorless semi-solid (77.8 mg, 78%): IR (neat) 3381, 2936, 1769, 1742, 1678, 1511, 1246, 1111 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.47 (d, J=7.3 Hz, 1H), 8.31 (d, J=5.4 Hz, 1H), 7.09 (d, J=8.6 Hz, 2H), 6.98 (d, J=5.5 Hz, 1H), 6.83 (d, J=8.6 Hz, 2H), 4.91 (dq, J=9.1, 6.4 Hz, 1H), 4.55 (ddd, J=10.9, 8.4, 7.0 Hz, 1H), 3.88 (s, 3H), 3.81 (t, J=6.6 Hz, 2H), 3.78 (s, 3H), 3.57 (dd, J=9.7, 7.0 Hz, 1H), 3.44 (dd, J=9.7, 6.8 Hz, 1H), 3.41 (s, 3H), 3.15 (t, J=9.0 Hz, 1H), 3.07 (dd, J=13.4, 3.3 Hz, 1H), 2.98 (t, J=6.6 Hz, 2H), 2.35-2.20 (m, 2H), 1.87-1.77 (m, 1H), 1.61-1.47 (m, 2H), 1.48-1.37 (m, 1H), 1.45 (d, J=6.4 Hz, 3H), 1.22-1.05 (m, 2H), 0.90-0.79 (m, 1H), 0.63-0.49 (m, 2H), 0.29-0.14 (m, 2H); 13C NMR (101 MHz, CDCl3) δ 172.61, 169.39, 162.32, 159.40, 157.82, 146.76, 141.45, 137.29, 132.66, 129.73, 113.77, 109.78, 83.79, 78.71, 75.22, 67.58, 58.78, 56.30, 55.22, 51.47, 46.17, 35.92, 34.62, 33.89, 26.55, 18.73, 18.08, 11.18, 3.16, 3.00; HRMS-ESI (m/z) ([M]+) calcd for C32H42N2O9, 598.2890; found, 598.2914.
