反应详情

To a solution of ethyl 3-{2-fluoro-4-[(4′-hydroxy-2′,6′-dimethylbiphenyl-3-yl)methoxy]phenyl}propanoate (315 mg, 0.74 mmol) in N,N-dimethylformamide (4 mL) was added sodium hydride (60%, 31 mg, 0.78 mmol) at 0° C. with stirring, and the mixture was stirred at room temperature for 30 min. Diethyl (3-bromopropyl)phosphonate (578 mg, 2.23 mmol) and potassium iodide (37 mg, 0.22 mmol) were added, and the mixture was further stirred overnight at 60° C. The reaction mixture was concentrated under reduced pressure. Brine was added to the residue, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-1/4) and then by preparative HPLC (gradient cycle A) to give the title compound (0.22 g, yield 50%) as a colorless oil.

1. stirringthe mixture was stirred at room temperature for 30 min
2. stirringthe mixture was further stirred overnight at 60° C
3. concentrationThe reaction mixture was concentrated under reduced pressure
4. additionBrine was added to the residue
5. extractionthe mixture was extracted with ethyl acetate
6. dry with materialThe extract was dried over anhydrous sodium sulfate
7. concentrationconcentrated under reduced pressure
8. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-1/4)