反应详情

温度

80 °C

Sodium carbonate (96 g, 909.79 mmol) was added to benzyl 4-(trifluoromethylsulfonyloxy)-5,6-dihydropyridine-1(2H)-carboxylate (123.1 g, 303.26 mmol) and 4-hydroxyphenylboronic acid (46.0 g, 333.59 mmol) in a mixture of dioxane (1000 mL) and water (250 mL). The resulting mixture was bubbled with nitrogen for 10 minutes then 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium(II) (5.49 g, 7.58 mmol) was added and the reaction mixture was heated at 80° C. for 1 hour, then cooled to room temperature. The reaction mixture was diluted with DCM (2 L) and washed with water (2 L). The aqueous washing was re-extracted with DCM (1 L), then the combined organics were washed with saturated brine (500 mL), dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 10 to 30% EtOAc in isohexane. Fractions containing the desired product were evaporated to dryness then triturated with isohexane, filtered and dried to afford benzyl 4-(4-hydroxyphenyl)-5,6-dihydropyridine-1(2H)-carboxylate (62.3 g, 66.4%) as a solid.

1. customThe resulting mixture was bubbled with nitrogen for 10 minutes
2. temperaturecooled to room temperature
3. washwashed with water (2 L)
4. washThe aqueous washing
5. extractionwas re-extracted with DCM (1 L)
6. washthe combined organics were washed with saturated brine (500 mL)
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. customevaporated
10. customto afford crude product
11. customThe crude product was purified by flash silica chromatography, elution gradient 10 to 30% EtOAc in isohexane
12. additionFractions containing the desired product
13. customwere evaporated to dryness
14. customthen triturated with isohexane
15. filtrationfiltered
16. customdried