反应详情

温度

60 °C

H2O2 (30% in H2O; 153 μL, 1.5 mmol) was added to a stirred solution of gefitinib 4d (223 mg, 0.5 mmol), concentrated H2SO4 (80 μL, 1.5 mmol), 3-iodooxetane (183 mg, 1.0 mmol) and iron(II) sulfate heptahydrate (42 mg, 0.15 mmol) in DMSO (5 mL) at 60 °C. After 1-2 min a further portion of iron(II) sulfate heptahydrate (50 mg, 0.18 mmol) was added, followed by dropwise addition of further H2O2 (30% in H2O; 153 μL, 1.5 mmol) over 5 min. The mixture was stirred at 60 °C for 30 min. After allowing to cool, the mixture was poured into a 0.2 M solution of NaOH which had been saturated with solid NaCl (30 mL) and EtOAc (50 mL). The aqueous and organic layers were partitioned and the aqueous layer was extracted with EtOAc (1 x 30 mL). The combined organic layers were dried (Na2SO4), filtered and the solvent removed under vacuum to leave a crude residue (ca. 300 mg). The residue was purified by high-performance liquid chromatography (column: Gemini C18; size: 250 x 21.2 mm; eluent: 70-90% MeOH in 10 mM aqueous Et2NH or 75% MeOH in 10 mM aqueous Et2NH; run time: 25 min; detection: UV at 254 nM) to give the desired product 5f (35 mg, 93% pure, 13% yield adjusted for purity). An analytical portion of the product 5f was triturated with hot EtOAc / hexanes to - 21 -give material for data purposes