Hydrochloric Acid → Treprostinil

反応式

[OH:1][C@H:2]1[C@H:18]([CH2:19][CH2:20][C@@H:21]([OH:27])[CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])[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]#N)[CH:10]=[CH:9][CH:8]=3.[OH-:28].[K+].Cl.C[OH:32]>>[CH3:26][CH2:25][CH2:24][CH2:23][CH2:22][C@H:21]([OH:27])[CH2:20][CH2:19][C@H:18]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:32])=[O:28])[CH:10]=[CH:9][CH:8]=1

参加物

反応物 4

HCID 313Hydrochloric Acid

HCID 887Methanol

HCID 14797Potassium Hydroxide

HCID 11314741Descarboxymethyl Cyanomethyl Treprostinil

生成物 1

HCID 6918140Treprostinil収率 81%

反応条件

温度: 10 °C

実験手順

2-((1R,2R,3aS,9aS)-2,3,3a,4,9,9a-hexahydro-2-hydroxy-1-((S)-3-hydroxyoctyl)-1H-cyclopent a[b]naphthalen-5-yloxy)acetonitrile (2 g, 0.005 mmol) in methanol (18 ml) was treated with 20% KOH (6 ml) and refluxed for 3 hr. The reaction was then cooled to 10° C. and 3N HCl was added slowly until pH=˜8. The solvent was removed in vacuo. Ethyl acetate and brine were added and then 3N HCl was added slowly until pH=2. The reaction mixture was extracted with ethyl acetate. The combined ethyl acetate extracts were dried over anhydrous magnesium sulfate. The solid was filtered off. The solvent was evaporated off under vacuum. The crude product was purified by crystallization from ethanol/H2O. The titled compound was obtained in a crystalline form. Yield: 81%.