反应详情

温度

-70 °C

Combine tert-butyl 4-(4-iodo-1-(2-(pyrrolidin-1-yl)ethyl)-1H-imidazol-2-yl)piperidine-1-carboxylate (40.00 g, 82.63 mmol) and tetrahydrofuran (600 mL). Cool to −70° C. under nitrogen. Add 2.5 M n-butyllithium in hexanes (67.76 mL, 2.1 eq) dropwise. Add acetaldehyde (23.22 mL, 5.0 eq) and stir for 15 minutes. Quench over aqueous saturated ammonium chloride (75 mL). Separate the layers. Wash the aqueous phase with methyl tert-butyl ether. Wash the organics with water and aqueous saturated sodium chloride. Dry the organics over anhydrous magnesium sulfate, filter, and concentrate in vacuo. Dissolve in ethanol. Add 85% aqueous phosphoric acid dropwise to achieve a suspension. Stir the mixture overnight at room temperature. Filter and dry the resulting off-white solid under vacuum to give tert-butyl 4-(4-(1-hydroxyethyl)-1-(2-(pyrrolidin-1-yl)ethyl)-1H-imidazol-2-yl)piperidine-1-carboxylate; phosphoric acid (28.00 g, 69%). MS (ES) m/z=393 [M]+.

1. customQuench over aqueous saturated ammonium chloride (75 mL)
2. customSeparate the layers
3. washWash the aqueous phase with methyl tert-butyl ether
4. washWash the organics with water and aqueous saturated sodium chloride
5. dry with materialDry the organics over anhydrous magnesium sulfate
6. filtrationfilter
7. concentrationconcentrate in vacuo
8. dissolutionDissolve in ethanol
9. additionAdd 85% aqueous phosphoric acid dropwise
10. filtrationFilter
11. customdry the resulting off-white solid under vacuum