反应详情

温度

-10 °C

A 2-L, 3-neck flask was charged with (4-bromo-2-fluorophenyl)acetonitrile (100.91 g, 0.4715 mol), MeOTs (156 mL g, 1.034 mol), DMF (400 mL) and THF (400 mL). The headspace was purged with nitrogen and the solution was cooled to −10° C. The NaOtBu (96.58 g, 1.005 mol) was divided into 4 equal portions that were added separately to the reaction to control the exotherm. Five minutes after the fourth and final charge an aliquot was removed and analyzed by HPLC, verifying reaction completion. The cold bath was removed, and the reaction allowed to stir without cooling (internal temp =4° C.). The flask was then charged with DABCO (13.02 g, 0.116 mol) to consume the remaining MeOTs. After 30 min an aliquot was removed and analyzed by HPLC, showing no detectable MeOTs. The flask was charged with H2O (400 mL) and hexanes (400 mL) and the mixture added to a separatory funnel. The phases were mixed well and then separated. The aqueous phase was re-charged to the separatory funnel and re-extracted with hexanes (200 mL). The organic phases from the first two extractions were combined and transferred back to the separatory funnel and washed twice with H2O (200 mL). The phases were separated and the organic layer was added to a 2-L, 3-neck flask set up for distillation. The solution was distilled under vacuum (400 torr with an internal temperature of about 50° C.) until no significant solvent distillation occurred. An aliquot of the solution was removed and analyzed by 1H NMR to record the amount of solvents present. The solution of product was held overnight and used without further processing in the next step.

1. customThe headspace was purged with nitrogen
2. additionwere added separately to the reaction
3. additionFive minutes after the fourth and final charge an aliquot
4. customwas removed
5. customreaction completion
6. customThe cold bath was removed
7. temperaturewithout cooling (internal temp =4° C.)
8. customto consume the remaining MeOTs
9. customAfter 30 min an aliquot was removed
10. additionThe flask was charged with H2O (400 mL) and hexanes (400 mL)
11. additionthe mixture added to a separatory funnel
12. additionThe phases were mixed well
13. customseparated
14. additionThe aqueous phase was re-charged to the separatory funnel
15. extractionre-extracted with hexanes (200 mL)
16. extractionThe organic phases from the first two extractions
17. washwashed twice with H2O (200 mL)
18. customThe phases were separated
19. additionthe organic layer was added to a 2-L, 3-neck flask
20. distillationset up for distillation
21. distillationThe solution was distilled under vacuum (400 torr with an internal temperature of about 50° C.)
22. distillationuntil no significant solvent distillation
23. customAn aliquot of the solution was removed