Reaktion #67896

ord-992ff0b0d22e428187215eb9bc66567b

Reaktionsgleichung

CCCCC[C@H](O)/C=C/[C@@H]1[C@H]2Cc3cccc(OCC(=O)O)c3C[C@H]2C[C@H]1O
2-((1R,2R,3aS,9aS)-2,3,3a,4,9,9a-hexahydro-2-hydroxy-1-((S,E)-3-hydroxyoct-1-enyl)-1H-cyclopenta[b]naphthalen-5-yloxy)acetic acid
[K+].[OH-]
potassium hydroxide
→
CCCCC[C@H](O)CC[C@@H]1[C@H]2Cc3cccc(OCC(=O)O)c3C[C@H]2C[C@H]1O
titled compound
Ausbeute 88.0%
CCCCC[C@H](O)CC[C@@H]1[C@H]2Cc3cccc(OCC(=O)O)c3C[C@H]2C[C@H]1O
Treprostinil
Ausbeute 88.0%

Edukte

CCCCC[C@H](O)/C=C/[C@@H]1[C@H]2Cc3cccc(OCC(=O)O)c3C[C@H]2C[C@H]1O
2-((1R,2R,3aS,9aS)-2,3,3a,4,9,9a-hexahydro-2-hydroxy-1-((S,E)-3-hydroxyoct-1-enyl)-1H-cyclopenta[b]naphthalen-5-yloxy)acetic acid
[K+].[OH-]
potassium hydroxide

Reagenzien

[Pd]
Pd/C

Lösungsmittel

CO
methanol

Reaktionsbedingungen

Detaillierte Bedingungen
See reaction.notes.procedure_details.

Aufarbeitung

  1. 1
    Sonstigeovernight
  2. 2
    Sonstigeat room temperature
  3. 3
    FiltrationThen, the reaction mixture was filtered with celite pad
  4. 4
    SonstigeThe solvent was evaporated off under vacuum
  5. 5
    workup.ADDITIONThe residues was diluted with 50 m ethyl acetate and 50 ml saturated sodium bicarbonate aqueous
  6. 6
    Sonstigeseparated
  7. 7
    Extraktionthe organic layers was extracted with 50 ml saturated sodium bicarbonate aqueous
  8. 8
    workup.ADDITION3N HCl was added slowly until pH=˜2
  9. 9
    ExtraktionThe aqueous layer was extracted with 100 ml ethyl acetate
  10. 10
    Trocknendried over anhydrous magnesium sulfate
  11. 11
    FiltrationThe solid was filtered off
  12. 12
    SonstigeThe solvent was evaporated off under vacuum
  13. 13
    SonstigeThe crude product was purified by crystallization

Vorschrift

2-((1R,2R,3aS,9aS)-2,3,3a,4,9,9a-hexahydro-2-hydroxy-1-((S,E)-3-hydroxyoct-1-enyl)-1H-cyclopenta[b]naphthalen-5-yloxy)acetic acid (2.5 g, 0.008 mol) in dry methanol (25 ml) was treated with potassium hydroxide (0.5 g, 0.008 mol), then with 5% Pd/C (0.5 g, 20% wt) under hydrogen overnight at room temperature. Then, the reaction mixture was filtered with celite pad. The solvent was evaporated off under vacuum. The residues was diluted with 50 m ethyl acetate and 50 ml saturated sodium bicarbonate aqueous. The mixture was phase separated and the organic layers was extracted with 50 ml saturated sodium bicarbonate aqueous. The aqueous layers were combined and then 3N HCl was added slowly until pH=˜2. The aqueous layer was extracted with 100 ml ethyl acetate. The organic layers were combined and dried over anhydrous magnesium sulfate. The solid was filtered off. The solvent was evaporated off under vacuum. The crude product was purified by crystallization. The titled compound was obtained in a crystalline form. Yield: 88%

Quelle

DOI: 10.6084/m9.figshare.5104873.v1Patent: US08524939B2uspto-grants-2013_09