反应详情

A reaction mixture of 3-bromo-4-fluorobenzaldehyde (1.70 g, 8.37 mmol) and aminoacetaldehyde dimethyl acetal (0.917 mL, 8.37 mmol) in toluene (17.0 mL) was stirred at r.t. overnight. Then sulfuric acid (10 mL) and phosphorus pentoxide (2.38 g, 8.37 mmol) were added. The mixture was stirred at 160° C. for 1 h. After cooled, the mixture was poured into crushed ice. The acidic mixture was carefully adjusted to pH=8 by the addition of aqueous NaOH solution (1 N) with stirring and external cooling. The 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 40% ethyl acetate in hexanes to afford the desired product (0.35 g, 18.5%). LCMS (M+H)+: m/z=225.9/227.9.

1. stirringThe mixture was stirred at 160° C. for 1 h
2. temperatureAfter cooled
3. additionthe mixture was poured
4. custominto crushed ice
5. stirringwith stirring
6. extractionThe 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 40% ethyl acetate in hexanes