反应详情

The reaction was carried out under argon. 3-Fluoro-4-methylbenzonitrile (121 g, 895 mmol) and N,N-dimethylformamide dimethyl acetal (245 g, 2.06 mol) were dissolved in DMF (1.8 liters) and stirred under reflux overnight. The contents of the flask was then poured into water (2 liters), the mixture was extracted twice with ethyl acetate and the combined organic phases were washed with saturated sodium chloride solution. The organic phase was concentrated, and the residue was dissolved again in THF/water (1:1, 2.7 liters). Sodium periodate (503 g, 2.35 mol) was added, and the mixture was stirred at room temperature for one hour. The precipitate was then separated off, and the filtrate was recovered and extracted repeatedly with ethyl acetate. The combined organic phases were washed once with saturated sodium bicarbonate solution and once with saturated sodium chloride solution, dried and concentrated to give an oil. This was purified by column chromatography on silica gel (mobile phase: petroleum ether/dichloromethane 6:4, then 4:6, finally pure dichloromethane). The product fractions were concentrated. This gave 28.0 g (20% of theory) of the target compound as a white crystalline solid.

1. temperatureunder reflux overnight
2. extractionthe mixture was extracted twice with ethyl acetate
3. washthe combined organic phases were washed with saturated sodium chloride solution
4. concentrationThe organic phase was concentrated
5. dissolutionthe residue was dissolved again in THF/water (1:1, 2.7 liters)
6. stirringthe mixture was stirred at room temperature for one hour
7. customThe precipitate was then separated off
8. customthe filtrate was recovered
9. extractionextracted repeatedly with ethyl acetate
10. washThe combined organic phases were washed once with saturated sodium bicarbonate solution and once with saturated sodium chloride solution
11. customdried
12. concentrationconcentrated
13. customto give an oil
14. customThis was purified by column chromatography on silica gel (mobile phase
15. concentrationThe product fractions were concentrated