反应详情

温度

0 °C

To a solution of compound 3B (9.0 mg, 0.025 mmol) in DMF:THF (1:1, 1 mL) at 0° C. was added KOtBu (1.5 M in THF, 0.025 mL, 0.038 mmol). After stirring for 45° min at 0° C., methyl iodide (2 μL, 0.025 mmol) was added and the reaction mixture was stirred for an additional 1h, warmed to 25° C., and stirred for 3h. No reaction was observed during this time. The reaction mixture was cooled once more to 0° C., additional KOtBu (1.5 M in THF, 0.25 mL, 0.38 mmol) was added and the reaction mixture was stirred for 30 min, after which time additional methyl iodide (20 μL, 0.25 mmol) was added. After stirring for an additional 2h at 0° C., the reaction was quenched by the addition of saturated aqueous NH4Cl (10 mL) and dichloromethane (10 mL). The layers were separated, the aqueous phase was extracted with dichloromethane (2×10 mL) and the combined organic extracts were dried over MgSO4, filtered concentrated, and purified by preparative HPLC (YMC S5 ODS 20×100 mm, eluting with 30-100% aqueous methanol over 15 min containing 0.1% TFA, 20 mL/min) to afford the desired product as a yellow semi-solid. HPLC: 100% at 4.27 min (retention time) (YMC S5 ODS column, 4.6×50 mm, eluting with 10-90% aqueous methanol over 4 min containing 0.2% phosphoric acid, 4 mL/min, monitoring at 200 nm). MS (ES): m/z 385.21 [M+H]+.

1. temperaturewarmed to 25° C.
2. stirringstirred for 3h
3. temperatureThe reaction mixture was cooled once more to 0° C.
4. stirringthe reaction mixture was stirred for 30 min
5. customthe reaction was quenched by the addition of saturated aqueous NH4Cl (10 mL) and dichloromethane (10 mL)
6. customThe layers were separated
7. extractionthe aqueous phase was extracted with dichloromethane (2×10 mL)
8. dry with materialthe combined organic extracts were dried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated
11. custompurified by preparative HPLC (YMC S5 ODS 20×100 mm, eluting with 30-100% aqueous methanol over 15 min containing 0.1% TFA, 20 mL/min)