Phosphoric Acid → Disodium

Participants

Reaction Steps

A solution of Example 204A (2.46 mg, 3.2 mmol) in tetrahydrofuran (16.0 mL) was treated with 4 Å molecular sieves (8.0 g), a solution of phosphoric acid (32.0 mL, 0.5 M in DMF), and N-iodosuccinimide (1.45 g, 6.4 mmol) at 25° C. for 45 minutes. The mixture was poured into cold 10% sodium carbonate, diluted with methanol, filtered and through celite. The filtrate was decolorized with saturated sodium thiosulfate and concentrated. The resulting concentrate was dissolved in methanol, filtered and concentrated. Methanol and water were added to the resulting concentrate and the pH was adjusted to 9 by addition of 10% Na2CO3, and the mixture was purified by reverse phase HPLC using a C18 column, eluting with a gradient starting with water and ending with methanol, to give the title compound as a disodium salt (1.53 g, 56% yield). 1H NMR (300 MHz, MeOH-d4), δ ppm 0.80 (s, 9 H), 0.88 (s, 9 H), 1.67-1.76 (m, 1H), 2.00-2.10 (m, 1 H), 2.68-2.99 (m, 4 H), 3.54 (s, 3 H), 3.65 (s, 3 H), 3.70-3.74 (m, 1 H), 3.93 (s, 1 H), 3.94 (s, 1 H), 4.22-4.32 (m, 1 H), 4.34-4.38 (m, 1 H), 5.02 (dd, J=8.8, 5.5 Hz, 1 H), 5.15 (dd, J=8.8, 5.2 Hz, 1 H), 7.05-7.33 (m, 8 H), 7.77-7.89 (m, 4 H), 8.56 (m, 1 H).

Provenance & Evidence