Potassium Hydroxide → Treprostinil

HRID 245603

Reaction equation

HRID 245603 reaction equation
[OH:1][C@H:2]1[C@H:19](/[CH:20]=[CH:21]/[C@@H:22]([OH:28])[CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])[C@H:5]2[CH2:6][C:7]3[C:12]([CH2:13][C@H:4]2[CH2:3]1)=[C:11]([O:14][CH2:15][C:16]([OH:18])=[O:17])[CH:10]=[CH:9][CH:8]=3.[OH-].[K+]>CO.[Pd]>[CH3:27][CH2:26][CH2:25][CH2:24][CH2:23][C@H:22]([OH:28])[CH2:21][CH2:20][C@H:19]1[C@H:2]([OH:1])[CH2:3][C@H:4]2[C@@H:5]1[CH2:6][C:7]1[C:12]([CH2:13]2)=[C:11]([O:14][CH2:15][C:16]([OH:18])=[O:17])[CH:10]=[CH:9][CH:8]=1

Participants

5

Reactant 2

HCID 14797Potassium HydroxideHCID 712685732-((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

Product 1

HCID 6918140TreprostinilYield 88%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

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 nm 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%

Workup

  1. customovernight
  2. customat room temperature
  3. filtrationThen, the reaction mixture was filtered with celite pad
  4. customThe solvent was evaporated off under vacuum
  5. additionThe residues was diluted with 50 nm ethyl, acetate and 50 ml saturated sodium bicarbonate aqueous
  6. customseparated
  7. extractionthe organic layers was extracted with 50 ml saturated sodium bicarbonate aqueous
  8. addition3N HCl was added slowly until pH=˜2
  9. extractionThe aqueous layer was extracted with 100 ml ethyl acetate
  10. dry with materialdried over anhydrous magnesium sulfate
  11. filtrationThe solid was filtered off
  12. customThe solvent was evaporated off under vacuum
  13. customThe crude product was purified by crystallization

Sources & evidence

ORD record
ord-07838bb9c2c34183a21f60bf44159cb6
Source dataset
uspto-grants-2014_02
Patent number
US08658837B2

Linked notes

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