反应详情

温度

85 °C

1-(3-Bromo-5-chloro-4-fluoro-2-hydroxyphenyl)ethanone (2.0 g, 7.5 mmol, Example 43, Step 1) was combined with potassium cyanide (0.58 g, 9.0 mmol) in N,N-dimethylformamide (16 mL) and heated to 85° C. in an oil bath. After heating for 18 hrs, the reaction was allowed to cool to room temperature and iodomethane (0.90 mL, 11 mmol) and potassium carbonate (2.1 g, 15 mmol) were added. The reaction was heated to 65° C. and monitored by LC/MS. After heating for 3 hrs the reaction was complete and allowed to cool to room temperature, then taken up in ethyl acetate and washed with water, brine, and dried over magnesium sulfate. The resultant solution was concentrated to give the crude product as a dark oil. The product was purified by FCC on silica gel eluting hexane:ethyl acetate gradient to give 4-acetyl-2-bromo-6-chloro-3-methoxybenzonitrile (1.65 g, 75%) as a solid residue. LCMS calculated for C10H8BrClNO2(M+H)+: m/z=287.9, 289.9; found: 288.1, 290.0.

1. temperatureAfter heating for 18 hrs
2. temperatureto cool to room temperature
3. temperatureThe reaction was heated to 65° C.
4. temperatureAfter heating for 3 hrs the reaction
5. temperatureto cool to room temperature
6. washwashed with water, brine
7. dry with materialdried over magnesium sulfate
8. concentrationThe resultant solution was concentrated
9. customto give the crude product as a dark oil
10. customThe product was purified by FCC on silica gel
11. washeluting hexane