反应详情

A solution of tert-butyl (3R,5S)-3-(hydroxymethyl)-5-[{[1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]piperidine-1-carboxylate (208 mg), 1,3,4-triazole (52 mg), triphenylphosphine (262 mg) and diisopropyl azodicarboxylate (40% toluene solution, 632 mg) in THF (5 ml) was stirred at 50° C. for 15 hr. The reaction mixture was concentrated under reduced pressure, diluted with water and ethyl acetate, and the organic layer was separated. The organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, and a fraction eluted with ethyl acetate-hexane (1:5-1:0) and ethyl acetate-methanol (1:0-9:1) was concentrated under reduced pressure. The residue was subjected to basic silica gel column chromatography, and a fraction eluted with ethyl acetate-hexane (1:9 to 3:1) was concentrated under reduced pressure to give the object product (180 mg).

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. additiondiluted with water and ethyl acetate
3. customthe organic layer was separated
4. washThe organic layer was washed with saturated brine
5. dry with materialdried over anhydrous sodium sulfate
6. customThe solvent was evaporated under reduced pressure
7. washa fraction eluted with ethyl acetate-hexane (1:5-1:0) and ethyl acetate-methanol (1:0-9:1)
8. concentrationwas concentrated under reduced pressure
9. washa fraction eluted with ethyl acetate-hexane (1:9 to 3:1)
10. concentrationwas concentrated under reduced pressure