反应详情

Palladium tetrakis(triphenylphosphine) (69 mg, 0.06 mmol) was added to a degassed, ambient temperature solution of tert-butyl 2-[1-{[(benzyloxy)carbonyl]amino}-2-(4-bromophenyl)ethyl]-4-(2,2-dimethylbutyl)-1H-imidazole-1-carboxylate (for synthesis see Example 37) (324 mg, 0.60 mmol), 2-bromo-5-fluoropyridine (105 mg, 0.60 mmol) and hexamethylditin (195 mg, 0.60 mmol) in 1,4-dioxane (15 mL). After stirring at reflux overnight, the reaction mixture was diluted with water and extracted with methylene chloride and ethyl acetate. The combined organic extracts were dried (magnesium sulfate) and concentrated in vacuo. Triethylamine (0.25 mL, 1.79 mmol) followed by di-tert-butyl dicarbonate (260 mg, 1.19 mmol) were added to an ambient temperature solution of the crude residue and N,N-dimethylaminopyridine (catalytic). After stirring at ambient temperature for 1 h, the reaction mixture was quenched with water and extracted with methylene chloride. The combined organic extracts were dried (magnesium sulfate) and concentrated in vacuo. Chromatography over silica eluting with 0-50% ethyl acetate/hexane afforded tert-butyl 2-{1-{[(benzyloxy)carbonyl]amino}-2-[4-(5-fluoropyridin-2-yl)phenyl]ethyl}-4-(2,2-dimethylbutyl)-1H-imidazole-1-carboxylate.

1. temperatureat reflux overnight
2. extractionextracted with methylene chloride and ethyl acetate
3. dry with materialThe combined organic extracts were dried (magnesium sulfate)
4. concentrationconcentrated in vacuo
5. stirringAfter stirring at ambient temperature for 1 h
6. customthe reaction mixture was quenched with water
7. extractionextracted with methylene chloride
8. dry with materialThe combined organic extracts were dried (magnesium sulfate)
9. concentrationconcentrated in vacuo