反应详情

Add tert-butyl 4-(4-bromo-1-(2-hydroxyethyl)-1H-imidazol-2-yl)piperidine-1-carboxylate (42.00 g, 112.22 mmol) in 1,4-dioxane (400 mL) and water (200 mL). Add potassium phosphate, tribasic, N-hydrate (47.64 g, 2.0 eq) and dicyclohexyl-[2-(2,6-dimethoxyphenyl)phenyl]phosphane (5.76 g, 0.12 eq). Degas with nitrogen for 5 minutes. Add 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (30.25 mL, 1.5 eq) then degas for another 10 minutes. Add palladium acetate (1.26 g, 0.05 eq) and reflux at 120° C. overnight. Stop heating after 12 hrs. Filter through Celite®. Wash with dichloromethane and methanol. Concentrate to dryness in vacuo. Dilute with saturated aqueous sodium chloride then extract with ethyl acetate three times. Dry over anhydrous sodium sulfate and concentrate in vacuo. Purify by silica gel chromatography, eluting with 50-90% ethyl acetate/hexanes, to give the title compound as a yellow foam (20.50 g, 56%). MS (ES) m/z=322 [M]+.

1. customDegas with nitrogen for 5 minutes
2. temperatureStop heating after 12 hrs
3. filtrationFilter through Celite®
4. washWash with dichloromethane and methanol
5. concentrationConcentrate to dryness in vacuo
6. additionDilute with saturated aqueous sodium chloride
7. extractionthen extract with ethyl acetate three times
8. dry with materialDry over anhydrous sodium sulfate
9. concentrationconcentrate in vacuo
10. customPurify by silica gel chromatography
11. washeluting with 50-90% ethyl acetate/hexanes