反应详情

Combine 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (19.1 g, 1.6 eq), tert-butyl 4-[4-iodo-1-(2-pyrrolidin-1-ylethyl)imidazol-2-yl]piperidine-1-carboxylate (27 g, 56.9 mmol), sodium carbonate (120.6 g, 3.0 eq), and dimethyl sulfoxide (135 mL). Stir for five minutes. Add tri-tert-butylphosphonium tetrafluoroborate (1.7 g, 0.1 eq) and palladium(II) acetate (645.4 mg, 0.05 eq). Stir the resulting suspension at 75-80° C. under nitrogen for 45 minutes. Allow the mixture to cool to room temperature, then dilute with water (190 mL) and methyl tert-butyl ether (80 mL). Wash the aqueous layer with methyl tert-butyl ether (3×54 mL). Wash the organics with water (60 mL) and then with a 10% w/w aqueous solution of phosphoric acid (60 mL, 20 mL). Combine these aqueous layers and wash them with methyl tert-butyl ether (60 mL). Add sodium carbonate to the acidic aqueous layer to adjust the pH to 12. Wash the basic aqueous layer with methyl tert-butyl ether (120 mL, 30 mL). Wash the combined organics with aqueous saturated sodium chloride, dry over anhydrous magnesium sulfate, and concentrate in vacuo to give tert-butyl 4-[4-(3,6-dihydro-2H-pyran-4-yl)-1-(2-pyrrolidin-1-ylethyl)imidazol-2-yl]piperidine-1-carboxylate (23.6 g, 96%). MS (ES) m/z=431 [M]+.

1. stirringStir the resulting suspension at 75-80° C. under nitrogen for 45 minutes
2. washWash the aqueous layer with methyl tert-butyl ether (3×54 mL)
3. washWash the organics with water (60 mL)
4. washCombine these aqueous layers and wash them with methyl tert-butyl ether (60 mL)
5. washWash the basic aqueous layer with methyl tert-butyl ether (120 mL, 30 mL)
6. washWash the combined organics with aqueous saturated sodium chloride
7. dry with materialdry over anhydrous magnesium sulfate
8. concentrationconcentrate in vacuo