反应详情

温度

40 °C

A 3 L flange flask equipped with a thermometer, condensor, nitrogen line and overhead stirrer was heated at 40° C. (external) then charged with cyclohexanol (750 mL), disodium carbonate (129.8 g, 1.225 mol), 3-bromo-4-chloro-5-fluoro-pyridine (Hydrochloric Acid 18) (137.5 g, 556.8 mmol) and tert-butyl piperidine-4-carboxylate (123.8 g, 668.2 mmol) rinsed in with cyclohexanol (350 mL). Mixture was heated to 120° C. internal temperature overnight (18 h). Reaction mixture was removed from hotplate and allowed to cool to room temperature. Water (687.5 mL) and EtOAc (687.5 mL) were added, stirred for 10 mins then transferred to separating funnel Additional EtOAc (1.238 L) was added, mixed and aqueous phase was removed. Organic phase was further washed with water (687 mL), aqueous phase removed, organic layer collected. Aqueous phases were combined and back extracted with EtOAc (687.5 mL), aqueous layer removed and organic phase combined with other organics. Organics concentrated in vacuo (water bath temp=60° C., vacuum down to 2 mBar) leaving a viscous brown oil.

1. customA 3 L flange flask equipped with a thermometer, condensor, nitrogen line and overhead stirrer
2. washrinsed in with cyclohexanol (350 mL)
3. temperatureMixture was heated to 120° C. internal temperature overnight (18 h)
4. customReaction mixture
5. customwas removed from hotplate
6. temperatureto cool to room temperature
7. additionWater (687.5 mL) and EtOAc (687.5 mL) were added
8. customto separating funnel Additional EtOAc (1.238 L)
9. additionwas added
10. additionmixed
11. customaqueous phase was removed
12. washOrganic phase was further washed with water (687 mL), aqueous phase
13. customremoved
14. customorganic layer collected
15. extractionback extracted with EtOAc (687.5 mL), aqueous layer
16. customremoved
17. concentrationOrganics concentrated in vacuo (water bath temp=60° C., vacuum down to 2 mBar)
18. customleaving a viscous brown oil