反应详情

A reaction mixture of 3-bromo-4-fluorobenzaldehyde (1.70 g, 8.37 mmol) (Aldrich, Cat. #339547) and aminoacetaldehyde dimethyl acetal (0.917 mL, 8.37 mmol) (Aldrich, Cat. #121967) in toluene (17.0 mL) was stirred at r.t. overnight. The mixture was then added to sulfuric acid (10 mL) and phosphorus pentoxide (2.38 g, 8.37 mmol) at 160° C. The mixture was stirred at 160° C. for 1 h. After cooled to r.t., the mixture was poured onto crushed ice. The acidic mixture was adjusted to pH=8 by the careful addition of NaOH in water with stirring and external cooling. The basic mixture was extracted with ethyl acetate (3×200 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexanes (0-40%) to afford the desired product. Analytic LCMS (M+H)+: m/z=225.9/227.9.

1. stirringThe mixture was stirred at 160° C. for 1 h
2. temperatureAfter cooled to r.t.
3. additionthe mixture was poured
4. customonto crushed ice
5. stirringwith stirring
6. extractionThe basic mixture was extracted with ethyl acetate (3×200 mL)
7. washThe combined organic layers were washed with brine
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customThe residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexanes (0-40%)