Reaction Steps
To a mixture of 2-((3S,7R,8R,9S)-3-(3-hydroxy-4-methoxypicolinamido)-8-(isobutyryloxy)-9-methyl-2,6-dioxo-1,5-dioxonan-7-yl)ethyl benzoate (50 mg, 0.087 mmol), Na2CO3 (15 mg, 0.14 mmol) and NaI (3.09 mg, 0.021 mmol) in acetone (0.6 mL) was added chloromethyl isobutyrate (15.4 mg, 0.114 mmol) slowly at room temperature (about 22° C.). The resulting reaction mixture was warmed to 50° C. and stirred at 50° C. overnight. The solvent was evaporated and the crude residue was purified via flash chromatography (SiO2, hexanes/EtOAc gradient) to afford the title compound (35 mg, 76%) as an off-white solid: mp 48-50° C.; 1H NMR (300 MHz, CDCl3) δ 8.55 (d, J=7.9 Hz, 1H), 8.26 (d, J=5.5 Hz, 1H), 8.04-7.87 (m, 2H), 7.55 (t, J=7.4 Hz, 1H), 7.43 (t, J=7.5 Hz, 2H), 6.95 (d, J=5.4 Hz, 1H), 5.85-5.62 (m, 2H), 5.41 (s, 1H), 5.26-5.06 (m, 2H), 4.94 (dd, J=9.8, 6.3 Hz, 1H), 4.42-4.19 (m, 2H), 3.92 (d, J=14.3 Hz, 3H), 3.65 (s, 1H), 2.76 (t, J=9.5 Hz, 1H), 2.62 (dt, J=10.8, 5.5 Hz, 1H), 2.58-2.47 (m, 1H), 2.30 (s, 1H), 1.82 (s, 1H), 1.29 (d, J=6.3 Hz, 3H), 1.21 (dd, J=7.0, 0.9 Hz, 6H), 1.13 (d, J=7.0 Hz, 6H); ESIMS m/z 673 ([M+H]+).
