反应详情

温度

0 °C

To a stirred solution of 5-bromo-2,4-dimethoxypyrimidine (400 g, 1.826 mol) in anhydrous THF (3 L) under argon and cooled down to 0° C. was added dropwise TurboGrignard (1.821 L, 2.367 mol). The resulting mixture was stirred at 0° C. until exothermic ceased then, allowed to warm up and stir at RT for 30 min. A solution of di-tert-butyl azodicarboxylate in anhydrous THF (1 L) was added dropwise to the mixture and the reaction was stirred at RT for 1 hr. The reaction was slowly quenched with a saturated aq. NH4Cl solution (2 L), diluted with EtOAc (2 L) and water (2 L) and both phases separated. The aq. phase was extracted with EtOAc (3 L), combined organic layers were washed with brine (3 L), dried over Na2SO4, filtered and concentrated under reduced pressure. The resulting yellow oil was dissolved in Hexane (3 L) and the suspension was stirred at 0° C. for 3 hr, filtrated off and dried to afford a first batch of white crystals. The mother liquor was concentrated under reduced pressure and purified to afford a second batch of white crystals. The two batches were combined to afford the title product (507 g, 1.369 mol, 75% yield) as white crystals. tR: 1.03 min (LC-MS 1); ESI-MS: 371 [M+H]+, ESI-MS: 369 [M−H]− (LC-MS 1).

1. additionwas added dropwise TurboGrignard (1.821 L, 2.367 mol)
2. temperatureto warm up
3. stirringstir at RT for 30 min
4. stirringthe reaction was stirred at RT for 1 hr
5. customThe reaction was slowly quenched with a saturated aq. NH4Cl solution (2 L)
6. additiondiluted with EtOAc (2 L) and water (2 L)
7. customboth phases separated
8. extractionThe aq. phase was extracted with EtOAc (3 L)
9. washwere washed with brine (3 L)
10. dry with materialdried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated under reduced pressure
13. dissolutionThe resulting yellow oil was dissolved in Hexane (3 L)
14. stirringthe suspension was stirred at 0° C. for 3 hr
15. filtrationfiltrated off
16. customdried
17. customto afford a first batch of white crystals
18. concentrationThe mother liquor was concentrated under reduced pressure
19. custompurified
20. customto afford a second batch of white crystals