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4-Methylmorpholine → (S)-tert-Butyl 3-((tert-butoxycarbonyl)amino)-4-hydroxybutanoate

HRID 1908959
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HRID 1908959 반응식
[C:1]([O:5][C:6](=[O:20])[CH2:7][C@H:8]([NH:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C:9](O)=[O:10])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.C(OC(Cl)=O)C(C)C.[Cl-].[NH4+].S([O-])([O-])(=O)=O.[Mg+2]>O.C(OCC)(=O)C.O1CCCC1>[C:16]([O:15][C:13]([NH:12][C@H:8]([CH2:9][OH:10])[CH2:7][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:20])=[O:14])([CH3:18])([CH3:17])[CH3:19]
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참가 물질

9

반응물 5

HCID 79724-MethylmorpholineHCID 24083Sulfuric acid magnesium salt (1:1)HCID 25517Ammonium ChlorideHCID 62365Isobutyl chloroformateHCID 7010636Boc-Asp(OtBu)-OH

생성물 1

HCID 11616071(S)-tert-Butyl 3-((tert-butoxycarbonyl)amino)-4-hydroxybutanoate수율 97.7%

시약·촉매·용매 3

HCID 962Water용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

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온도
0 °C

실험 절차

2.0 g of (S)-4-t-butoxy-2-(t-butoxycarbonylamino)-4-oxobutanoic acid and 14 mL of tetrahydrofuran were added to 50 mL flask and then the resulting reaction solution was cooled to 0° C. While the reaction solution was stirred, 1.0 mL of 4-methylmorpholine was dropped, and after 10 minutes, 1.2 mL of isobutylchloroformate was dropped, and then stirred for 1 hour. The produced solid was filtered with diatomite, was washed with 14 mL of tetrahydrofuran, and then the filtrate was cooled to 0° C. 523 mg of sodium borohydride was added to the cooled filtrate, and stirred for 4 hours while the reaction temperature was naturally increased to room temperature. After completing the reaction, the reaction solution was cooled to 0° C. and then 10 mL of ammonium chloride aqueous solution was dropped. 20 mL of ethyl acetate and 10 mL of water were added and then stirred for 10 minutes. An organic layer was isolated, dehydrated with magnesium sulfate and then concentrated under reduced pressure. A concentrated residue was isolated with column chromatography (n-hexane:ethyl acetate=2:1) and then concentrated under reduced pressure to obtain 1.86 g of a title compound.

후처리

  1. customthe resulting reaction solution
  2. stirringstirred for 1 hour
  3. filtrationThe produced solid was filtered with diatomite
  4. washwas washed with 14 mL of tetrahydrofuran
  5. temperaturethe filtrate was cooled to 0° C
  6. addition523 mg of sodium borohydride was added to the cooled filtrate
  7. stirringstirred for 4 hours while the reaction temperature
  8. temperaturewas naturally increased to room temperature
  9. customthe reaction
  10. temperaturethe reaction solution was cooled to 0° C.
  11. stirringstirred for 10 minutes
  12. customAn organic layer was isolated
  13. concentrationconcentrated under reduced pressure
  14. customA concentrated residue was isolated with column chromatography (n-hexane:ethyl acetate=2:1)
  15. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-6c55e0ea2ac04a02b03a502cca4b2f1d
출처 데이터셋
uspto-grants-2013_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08598347B2

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