反应详情

In a 100-mL round-bottom flask under argon, 6-(3-methoxy-4-methoxymethoxy-phenyl)-1H-indazole (1.19 g, 4.18 mmol, 1 equiv) was dissolved in dioxane (25 mL) and 3N NaOH (14 mL). This mixture was treated with iodine (117 g, 14.60 mmol, 1.10 equiv) added in ˜5 portions (˜10 min). Several (˜4) additional portions of iodine (50 mg each) were added until the reaction was complete as visualized by TLC (3:7 ethyl acetate/hexane). The mixture was acidified with 20% citric acid (25 mL) and 5% NaHSO3 (20 mL) was added. The mixture was partioned between ethyl acetate (150 mL) and water (100 mL). Te organic material was washed with saturated sodium bicarbonate (80 ml) and bine (50 mL) and were dried over sodium sulfate and concentrated under reduced pressure. Purification by crystallization from ethyl acetate (3 mL) then hexane (7 ml) gave pure 3-iodo-6-(3-methoxy-4-methoxymethoxy-phenyl)-1H-indazole as a solid (1.33 g, 78 g): 1H NMR (CDCl3) δ 10.48 (bs, 1H), 7.62 (s, 1H), 7.57 (d, 1H, J=8.5 Hz), 7.47 (dd, 1H, J=1.3, 8.5 Hz), 7.18 (m, 3H), 5.29 (a, 2H), 3.99 (, 3H), 3.55 (s, 3H).

1. additionadded in ˜5 portions (˜10 min)
2. additionwas added
3. washTe organic material was washed with saturated sodium bicarbonate (80 ml) and bine (50 mL)
4. dry with materialwere dried over sodium sulfate
5. concentrationconcentrated under reduced pressure
6. customPurification
7. customby crystallization from ethyl acetate (3 mL)