反应详情

温度

-78 °C

To a stirring solution of 2 (76 mg, 0.195 mmol) and 4 (62 mg, 0.205 mmol, 1.05 eq) in THF (5 mL) at −78° C. was added freshly prepared 1M LDA dropwise (Prepared from Diisopropylamine and 2.5M n-Butyl Lithium in Hexanes). Upon addition of LDA, an orange color formed and stayed throughout the reaction. After 1.5 hr of stirring at −78° C. the reaction was quenched with 50% aqueous Acetic Acid (5 mL) and the reaction mixture warmed to room temperature. The reaction mixture was diluted with Ethyl Acetate (50 mL) and neutralized using 28-30% Ammonium Hydroxide (aq) until pH˜9. The aqueous layer was extracted one additional time with Ethyl Acetate and the combined organics washed with brine, dried (Na2SO4), and concentrated to a yellow crystalline solid. The crude mixture was purified using Biotage MPLC system (25S column size, 0-10% Methanol/CH2Cl2 over 70CV), giving title compound as an off white solid (60 mg, 0.100 mmol, 51%). 1H NMR (DMSO-d6, 400 MHz): δ 13.9 (s, 1H), δ 9.44 (s, 1H), δ 8.84-8.82 (d, 1H), δ 8.57 (s, 1H), δ 8.39-8.37 (d, 1H), δ 8.27-8.25 (d, 1H), δ 7.90 (bs, 1H), 7.79-7.64 (m, 3H), 7.50-7.35 (m, 1H), δ 7.30-7.28 (d, 1H), δ 3.70-3.30 (m, 8H), δ 2.46 (s, 3H), δ 1.41 (s, 9H); LRMS (m/z): 601 (M+H), 545

1. customan orange color formed
2. customstayed throughout the reaction
3. customwas quenched with 50% aqueous Acetic Acid (5 mL)
4. temperaturethe reaction mixture warmed to room temperature
5. additionThe reaction mixture was diluted with Ethyl Acetate (50 mL)
6. extractionThe aqueous layer was extracted one additional time with Ethyl Acetate
7. washthe combined organics washed with brine
8. dry with materialdried (Na2SO4)
9. concentrationconcentrated to a yellow crystalline solid
10. customThe crude mixture was purified