反应详情

温度

2.5 °C

Sodium hydride (225.6 g, 5.64 mol) is dispersed into THF (3 L) and the temperature is lowered to 0-5° C. A solution of (R)-3-hydroxy-1-boc piperidine (891.6 g, 4.43 mol) in THF (3 L) is added over 1 h while maintaining the temperature between 0-5° C. The reaction is stirred for 1 h. 2,6-Dichloropyrazine (600 g, 4.03 mol) as a solution in THE (3 L) is added dropwise over 1.5 h maintaining the same temperature. The reaction is stirred for 2 h at 25-30° C., and then poured onto ice. The mixture is diluted with water and extracted with ethyl acetate. The extracts are dried over anhydrous sodium sulfate, filtered, and concentrated. The residual oil is triturated with 5% dichloromethane in hexane to give the product as a white solid. The solid is collected by filtration and dried, to give 1538 g crude material. The crude product is retriturated with 5% dichloromethane in hexanes to give a white solid in quantitative yield. ES/MS m/z 314.1 [M+H]+.

1. customis lowered to 0-5° C
2. temperaturemaintaining the same temperature
3. stirringThe reaction is stirred for 2 h at 25-30° C.
4. additionpoured onto ice
5. extractionextracted with ethyl acetate
6. dry with materialThe extracts are dried over anhydrous sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residual oil is triturated with 5% dichloromethane in hexane