反应详情

温度

-20 °C

To 35.1 g of 2-bromo-3,5-dichloropyridine in 10 ml of tetrahydrofuran, 116.3 ml of a 1.3 M tetrahydrofuran solution of isopropylmagnesium chloride-lithium chloride complex was added dropwise with stirring at −20° C., and after the addition, the mixture was stirred at the same temperature for 15 minutes. Then, to the reaction mixture, 15.0 g of N-methoxy-N-methyl-2-(tert-butoxycarbonylamino)acetamide in 114 ml of tetrahydrofuran was added dropwise, and after the addition, the mixture was stirred at the same temperature for another 2 hours. After completion of the reaction, the reaction mixture was mixed with 100 ml of saturated aqueous ammonium chloride and 100 ml of water and extracted with ethyl acetate (200 ml×2), the resulting organic layers were combined, washed with water (100 ml×1) and dried over saturated aqueous sodium chloride and then anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography using ethyl acetate-hexane (with a gradient of from 0:10 to 3:7) as the eluent to obtain 12.5 g of the desired product as pale yellow crystals.

1. additionafter the addition
2. stirringthe mixture was stirred at the same temperature for 15 minutes
3. additionafter the addition
4. stirringthe mixture was stirred at the same temperature for another 2 hours
5. customAfter completion of the reaction
6. extractionextracted with ethyl acetate (200 ml×2)
7. washwashed with water (100 ml×1)
8. dry with materialdried over saturated aqueous sodium chloride
9. customanhydrous sodium sulfate, and the solvent was evaporated under reduced pressure
10. customThe resulting residue was purified by silica gel column chromatography