反应详情

tert-Butyl (3S, 5R)-3-{(1H-benzimidazol-2-ylcarbonyl)(2-methylpropyl)amino}-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate (700 mg), 3-methoxypropan-1-ol (123 mg) and triphenylphosphine (465 mg) were dissolved in THF (20 ml), diisopropyl azodicarboxylate (40% toluene solution: 896 mg) was added, and the mixture was stirred at room temperature for 60 hr. The reaction mixture was diluted with water, and the mixture was extracted with ethyl acetate. The extract was saturated aqueous sodium hydrogen carbonate and saturated washed with 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 (1:9-1:3) was concentrated under reduced pressure. The obtained substance was dissolved in ethyl acetate (3 ml), 4M hydrogen chloride-ethyl acetate (3 ml) was added, and the mixture was stirred at room temperature for 15 hr. The reaction mixture was basified with saturated aqueous sodium hydrogen carbonate, and extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to basic silica gel column chromatography, and a fraction eluted with ethyl acetate-hexane (1:9-1:0) and ethyl acetate-methanol (93:7) was concentrated under reduced pressure. The obtained substance was dissolved in ethyl acetate (10 ml), sulfuric acid (42 mg) was added, and the solvent was evaporated under reduced pressure. The residue was dissolved in ethanol (10 ml), and the solvent was evaporated under reduced pressure. The residue was crystallized from ethyl acetate-methanol to give the object product (180 mg) as crystals.

1. extractionthe mixture was extracted with ethyl acetate
2. washsaturated washed with brine
3. dry with materialdried over anhydrous sodium sulfate
4. customThe solvent was evaporated under reduced pressure
5. washa fraction eluted with ethyl acetate-hexane (1:9-1:3)
6. concentrationwas concentrated under reduced pressure
7. dissolutionThe obtained substance was dissolved in ethyl acetate (3 ml)
8. addition4M hydrogen chloride-ethyl acetate (3 ml) was added
9. stirringthe mixture was stirred at room temperature for 15 hr
10. extractionextracted with ethyl acetate
11. dry with materialThe extract was dried over anhydrous sodium sulfate
12. customThe solvent was evaporated under reduced pressure
13. washa fraction eluted with ethyl acetate-hexane (1:9-1:0) and ethyl acetate-methanol (93:7)
14. concentrationwas concentrated under reduced pressure
15. dissolutionThe obtained substance was dissolved in ethyl acetate (10 ml)
16. additionsulfuric acid (42 mg) was added
17. customthe solvent was evaporated under reduced pressure
18. dissolutionThe residue was dissolved in ethanol (10 ml)
19. customthe solvent was evaporated under reduced pressure
20. customThe residue was crystallized from ethyl acetate-methanol