Sodium Hydroxide → Simvastatin

HRID 381708

Reaktionsgleichung

[CH3:1][CH2:2][C:3]([C:6]([O:8][C@@H:9]1[C@@H:14]2[C@@H:15]([CH2:20][CH2:21][C@H:22]3[O:28][C:26](=[O:27])[CH2:25][C@H:24]([OH:29])[CH2:23]3)[C@@H:16]([CH3:19])[CH:17]=[CH:18][C:13]2=[CH:12][C@H:11]([CH3:30])[CH2:10]1)=[O:7])([CH3:5])[CH3:4].C([NH-])CCC.[OH-].[Na+]>>[CH3:1][CH2:2][C:3]([C:6]([O:8][C@@H:9]1[C@@H:14]2[C@@H:15]([CH2:20][CH2:21][C@H:22]3[O:28][C:26](=[O:27])[CH2:25][C@H:24]([OH:29])[CH2:23]3)[C@@H:16]([CH3:19])[CH:17]=[CH:18][C:13]2=[CH:12][C@H:11]([CH3:30])[CH2:10]1)=[O:7])([CH3:5])[CH3:4]

Komponenten

Edukt 2

HCID 14798Sodium Hydroxide

HCID 86584094Simvastatin butylamide

Produkt 1

HCID 54454Simvastatin

Versuchsvorschrift

In U.S. Pat. No. 4,820,850 (89)/CA 1,287,063 (91, Merck), lovastatin is reacted with butylamine to produce lovastatin butylarnide. The two hydroxy groups in the butylamide are protected with tert-butyldimethylsilyl chloride to produce a disilylated lovastatin butylamide. The disilylated lovastatin butylamide is enolized with lithium pyrrolidide and the enolate is alkylated with methyl iodide to produce a disilylated simvastatin butylamide on aqueous workup. The silyl protecting groups are removed using hydrofluoric acid to produce simvastatin butylamide. The simvastatin butylamide is hydrolyzed using sodium hydroxide and, following acidification, the dihydroxy acid form of simvastatin is obtained. The dihydroxy acid compound is reacted with ammonium hydroxide to produce an ammonium salt which is then relactonized by heating to produce simvastatin.

Quellen und Nachweise

ORD-Eintrag: ord-a7a6f4931e724887896d28b158e72162
Quelldatensatz: uspto-grants-2001_10
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US06307066B1

Verknüpfte Notizen

Wird geladen…