反应详情

To 4.2 g of potassium tert-butoxide in 72 ml of N,N-dimethylformamide, 7.8 g of 5-bromo-3-chloro-2-(nitromethyl)pyridine was added dropwise with stirring under cooling with ice, and after the addition, the mixture was stirred at the same temperature for another 1 hour. Then, to the reaction mixture, 4.7 g of the N-chloromethyl-2-(trifluoromethyl)benzamide prepared in Step 2 in Synthetic Example 19 in 30 ml of N,N-dimethylformamide was added dropwise with stirring under cooling with ice, and after the addition, the mixture was stirred at room temperature for another 2 hours. After completion of the reaction, the reaction mixture was carefully poured into 100 ml of ice-water, acidified with 10% aqueous hydrochloric acid and extracted with ethyl acetate (100 ml×2). The resulting organic layers were combined, washed with water (100 ml×2) and dried over saturated aqueous sodium chloride and then anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The resulting residue was purified by silica gel column chromatography using ethyl acetate-hexane (with a gradient of from 5:95 to 50:50) as the eluent to obtain 6.0 g of the desired product as a pale yellow oil.

1. temperatureunder cooling with ice
2. additionafter the addition
3. stirringthe mixture was stirred at the same temperature for another 1 hour
4. stirringwith stirring
5. temperatureunder cooling with ice
6. additionafter the addition
7. stirringthe mixture was stirred at room temperature for another 2 hours
8. customAfter completion of the reaction
9. extractionextracted with ethyl acetate (100 ml×2)
10. washwashed with water (100 ml×2)
11. dry with materialdried over saturated aqueous sodium chloride
12. distillationanhydrous sodium sulfate, and the solvent was distilled off under reduced pressure
13. customThe resulting residue was purified by silica gel column chromatography