Hydrochloric Acid → (R)-2-Benzyloxy-4-benzyloxycarbonylaminobutyric Acid

HRID 44159Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 44159
[CH2:1]([O:8][C:9]([NH:11][CH2:12][CH2:13][C@@H:14]([OH:18])[C:15]([OH:17])=[O:16])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O-2].[Ba+2].O.O.O.O.O.O.O.O.[OH-].[Ba+2].[OH-].[CH2:32](Br)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.Cl>CN(C)C=O.C(Cl)(Cl)Cl.O>[CH2:32]([O:18][C@H:14]([CH2:13][CH2:12][NH:11][C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:10])[C:15]([OH:17])=[O:16])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Komponenten

9

Edukt 5

HCID 313Hydrochloric AcidHCID 7498Benzyl BromideHCID 7004002(R)-4-(((Benzyloxy)carbonyl)amino)-2-hydroxybutanoic acidHCID 9855530Barium Oxide Nanoparticle DispersionHCID 17749109Barium hydroxide, octahydrate

Produkt 1

HCID 57784506(R)-2-Benzyloxy-4-benzyloxycarbonylaminobutyric AcidAusbeute 36 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittel2×HCID 6212ChloroformLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

4-Benzyloxycarbonylamino-2-(R)-hydroxybutyric acid (2.245 g) synthesized according to the method of H. Naito et al. (J. Antibiot., Vol. 26, pp. 297-301 (1973)) was dissolved in 25.6 mL of N,N-dimethylformamide. Barium oxide (6.795 g) was added to the solution under ice cooling with stirring, and the mixture was vigorously stirred for 2 min. Barium hydroxide octahydrate (5.593 g) was added to the reaction mixture, and the mixture was vigorously stirred under ice cooling for 10 min. Benzyl bromide (3.16 mL) was added thereto, and the mixture was vigorously stirred under ice cooling for 5 min. The reaction mixture was returned to room temperature and was vigorously stirred for 1.5 hr. Water (0.48 mL) was added under ice cooling, and the mixture was diluted with 70 mL of chloroform. 4 M hydrochloric acid (31 mL) was added to the diluted solution. Water (11 mL) was then added thereto followed by separation. The water layer was extracted with 22 mL+10 mL of chloroform. The combined organic layers were washed with 30 mL of saturated brine, were dried over magnesium sulfate and were concentrated to dryness to give 4.54 g of a crude product. The product was purified by column chromatography on 70 g of a neutral silica gel (chloroform→chloroform:ethyl acetate=4:1→chloroform:methanol=10:1→chloroform:methanol-acetic acid=10:1:0.1) to give the title compound (1.107 g, 36%).

Aufarbeitung

  1. stirringthe mixture was vigorously stirred for 2 min
  2. stirringthe mixture was vigorously stirred under ice cooling for 10 min
  3. stirringthe mixture was vigorously stirred under ice cooling for 5 min
  4. customwas returned to room temperature
  5. stirringwas vigorously stirred for 1.5 hr
  6. customthereto followed by separation
  7. extractionThe water layer was extracted with 22 mL+10 mL of chloroform
  8. washThe combined organic layers were washed with 30 mL of saturated brine
  9. dry with materialwere dried over magnesium sulfate
  10. concentrationwere concentrated to dryness
  11. customto give 4.54 g of a crude product
  12. customThe product was purified by column chromatography on 70 g of a neutral silica gel (chloroform→chloroform:ethyl acetate=4:1→chloroform:methanol=10:1→chloroform:methanol-acetic acid=10:1:0.1)

Quellen und Nachweise

ORD-Eintrag
ord-be54579bd1bb4c09ab59f715d321092c
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08541394B2

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