反应详情

温度

0 °C

Ethyl N-[2-[(2,2-dimethyl-1,3-dioxan-5-yl)amino]-6-(methyloxy)-3-pyridinyl]glycinate (35.42 g, 104.4 mmol) was dissolved in dry THF (500 ml) and the solution was added dropwise over 2 hours to a cooled (0° C.) suspension of sodium hydride (4.173 g of 60% w:w dispersion in oil, 1.00 eq.) in dry THF (500 ml) under argon. During the addition the colour of the suspension changed from orange to green. The mixture was stirred at 0° C. for a further 15 minutes, then allowed to warm to room temperature and stirred at rt for 1 hour. The mixture was cooled to 0° C. and saturated ammonium chloride (15 ml) was added cautiously with vigorous stirring (effervescence observed). After effervescence had ceased, the mixture was allowed to warm to room temperature and stirred for 4 hours then diluted with ethyl acetate (500 ml) and filtered with suction. The solids were washed with ethyl acetate (300 ml) and the combined filtrate plus washings were evaporated under reduced pressure to give a dark brown solid. This was stirred with petroleum ether) (40-60°) (500 ml) plus ethyl acetate (20 ml) for 2 h and filtered with suction to give a lighter brown solid which was washed with petroleum ether) (40-60°) (100 ml) and air-dried to afford the title compound as an amorphous tan solid (25.37 g, 82.8%).

1. additionthe solution was added dropwise over 2 hours to
2. temperaturea cooled
3. additionDuring the addition the colour of the suspension
4. temperatureto warm to room temperature
5. stirringstirred at rt for 1 hour
6. temperatureThe mixture was cooled to 0° C.
7. stirringwith vigorous stirring (effervescence observed)
8. temperatureto warm to room temperature
9. stirringstirred for 4 hours
10. filtrationfiltered with suction
11. washThe solids were washed with ethyl acetate (300 ml)
12. customthe combined filtrate plus washings were evaporated under reduced pressure
13. customto give a dark brown solid
14. filtrationfiltered with suction
15. customto give a lighter brown solid which
16. washwas washed with petroleum ether) (40-60°) (100 ml)
17. customair-dried