反应详情

温度

0 °C

To a slurry of the product from Example 207A (1.10 g, 1.39 mmol) and molecular sieves (4 Å, 3.5 g), in N,N-dimethylformamide (7.0 mL) at 0° C. were added a solution of phosphoric acid in N,N-dimethylformamide (13.0 mL, 0.5 M) and N-iodosuccinimide (0.626 g, 2.78 mmol), and the mixture was stirred at 0° C. for 4 hours. The reaction was treated with Na2S2O3 (saturated) and the pH was adjusted to 9 with 10% Na2CO3. The mixture was diluted with methanol and filtered through celite The methanol was evaporated and the mixture was purified by chromatography using a C18 column, eluting with a gradient starting with water and ending with methanol, to give the title compound as the disodium salt (0.70 g, 58% yield). 1H NMR (300 MHz, MeOH-d4), δ ppm 0.69 (s, 9 H), 0.93, 1.00 (2s, 9 H), 1.44 (d, J=5.2 Hz, 1.5 H), 1.47 (d, J=4.8 Hz, 1.5 H), 1.52-1.76 (m, 1H), 1.95-2.05 (m, 0.5 H), 2.30-2.40 (m, 0.5 H), 2.76-2.91 (m, 4 H), 3.58, 3.60 (2s, 3 H), 3.64 (s, 3 H), 3.84, 3.87 (2s, 1 H), 3.89-3.97 (m, 0.5 H), 4.03, 4.06 (2s, 1 H), 4.14-4.37 (m, 2.5 H), 5.34-5.41 (m, 0.5 H), 5.43-5.50 (m, 0.5 H), 7.02-7.19 (m, 5 H), 7.28-7.37 (m, 3 H), 7.77-7.89, (m, 4 H), 8.57 (m, 1 H).

1. filtrationfiltered through celite The methanol
2. customwas evaporated
3. customthe mixture was purified by chromatography
4. washeluting with a gradient