Phthalimide → HCID 58355421, compound

To a solution of tert-butyl (3S,5R)-3-{[(benzyloxy)carbonyl](2-methylpropyl)amino}-5-(hydroxymethyl)piperidine-1-carboxylate (0.47 g) in THF (15 ml) were added phthalimide (0.40 g), diisopropyl azodicarboxylate (1.59 g) and triphenylphosphine (0.66 g) at room temperature, and the mixture was stirred at room temperature for 15 hr. The reaction mixture was concentrated under reduced pressure, the residue was diluted with water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel chromatography, and a fraction eluted with ethyl acetate-hexane (1:9-1:2) was concentrated under reduced pressure. The obtained residue was dissolved in ethanol (10 ml), hydrazine hydrate (95 μl) was added, and the mixture was heated under reflux for 3 hr. The mixture was allowed to cool to room temperature, the precipitate was filtered off, and the filtrate was concentrated under reduced pressure. The residue was dissolved in THF (5 ml), diisopropylethylamine (0.29 μl) and 4-bromobutyryl chloride (0.16 ml) were added at 0° C., and the mixture was stirred at 0° C. for 1 hr. The reaction mixture was diluted with water, and extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was dissolved in THF (10 ml), potassium tert-butoxide (0.38 g) was added at 0° C., and the mixture was stirred at 0° C. for 1 hr. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel chromatography, and a fraction eluted with ethyl acetate-hexane (1:3-1:0) was concentrated under reduced pressure. The residue was dissolved in ethanol (10 ml), and 10% palladium-carbon (50% in water: 50 mg) was added. The reaction mixture was stirred under a hydrogen (normal pressure) at room temperature for 15 hr. The palladium catalyst was filtered off, and the filtrate was concentrated under reduced pressure to give the object product (0.30 g).

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. additionthe residue was diluted with water
3. extractionthe mixture was extracted with ethyl acetate
4. washThe extract was washed with saturated brine
5. dry with materialdried over anhydrous sodium sulfate
6. concentrationconcentrated under reduced pressure
7. washa fraction eluted with ethyl acetate-hexane (1:9-1:2)
8. concentrationwas concentrated under reduced pressure
9. dissolutionThe obtained residue was dissolved in ethanol (10 ml)
10. additionhydrazine hydrate (95 μl) was added
11. temperaturethe mixture was heated
12. temperatureunder reflux for 3 hr
13. temperatureto cool to room temperature
14. filtrationthe precipitate was filtered off
15. concentrationthe filtrate was concentrated under reduced pressure
16. dissolutionThe residue was dissolved in THF (5 ml)
17. additiondiisopropylethylamine (0.29 μl) and 4-bromobutyryl chloride (0.16 ml) were added at 0° C.
18. stirringthe mixture was stirred at 0° C. for 1 hr
19. additionThe reaction mixture was diluted with water
20. extractionextracted with ethyl acetate
21. washThe extract was washed with saturated brine
22. dry with materialdried over anhydrous sodium sulfate
23. concentrationconcentrated under reduced pressure
24. dissolutionThe residue was dissolved in THF (10 ml)
25. additionpotassium tert-butoxide (0.38 g) was added at 0° C.
26. stirringthe mixture was stirred at 0° C. for 1 hr
27. concentrationThe reaction mixture was concentrated under reduced pressure
28. additionthe residue was diluted with water
29. extractionthe mixture was extracted with ethyl acetate
30. washThe extract was washed with saturated brine
31. dry with materialdried over anhydrous sodium sulfate
32. concentrationconcentrated under reduced pressure
33. washa fraction eluted with ethyl acetate-hexane (1:3-1:0)
34. concentrationwas concentrated under reduced pressure
35. dissolutionThe residue was dissolved in ethanol (10 ml)
36. addition10% palladium-carbon (50% in water: 50 mg) was added
37. stirringThe reaction mixture was stirred under a hydrogen (normal pressure) at room temperature for 15 hr
38. filtrationThe palladium catalyst was filtered off
39. concentrationthe filtrate was concentrated under reduced pressure

ORD record

ord-e1f5c8715e1946b2b61ef08d2e4d8a29

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09221836B2