Isradipine → 2-Acetyl-3-benzofurazan-4-yl-acrylic acid methyl ester

HRID 2054702

Reaktionsgleichung

Reaktionsgleichung von HRID 2054702
[CH3:1][C:2]1NC(C)=C(C(OC(C)C)=O)[CH:4]([C:15]2[C:20]3=[N:21][O:22][N:23]=[C:19]3[CH:18]=[CH:17][CH:16]=2)[C:3]=1[C:24]([O:26][CH3:27])=[O:25].N1[O:29]N=C2C(C=O)=CC=CC=12.C(OC)(=O)CC(C)=O.N1CCCCC1>C(OC(C)C)(C)C.C(O)(=O)C>[CH3:27][O:26][C:24](=[O:25])[C:3]([C:2](=[O:29])[CH3:1])=[CH:4][C:15]1[C:20]2=[N:21][O:22][N:23]=[C:19]2[CH:18]=[CH:17][CH:16]=1

Komponenten

7

Edukt 4

HCID 3784IsradipineHCID 7757Methyl acetoacetateHCID 8082PiperidineHCID 102908732,1,3-Benzoxadiazole-4-carbaldehyde

Produkt 1

HCID 534332132-Acetyl-3-benzofurazan-4-yl-acrylic acid methyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 176Acetic AcidLösungsmittelHCID 7914Diisopropyl EtherLösungsmittel

Versuchsvorschrift

To achieve the afore-mentioned objects, the present invention provides for a process for the manufacture of the Isradipine which, involves two steps. In the first step 2,1,3-benzoxadiazole-4-carboxaldehyde is reacted with methyl acetoacetate in the presence of acetic acid and piperidine in diisopropyl ether. The product 2-acetyl-3-benzofurazan-4-yl-acrylic acid methyl ester is isolated and purified to get substantially high purity product with less than 0.3% 2,1,3-benzoxadiazole-4-carboxaldehyde content present in the purified product. In the second step the purified intermediate 2-acetyl-3-benzofurazan-4-yl-acrylic acid methyl ester is reacted with isopropyl-β-aminocrotonate in ethanol at 25 to 35° C. The crude Isradipine is crystallised from ethanol to get pure Isradipine having substantially higher purity and containing lower amount of the symmetrical ester isomers (III) and (IV).

Quellen und Nachweise

ORD-Eintrag
ord-391dc78fba9444bda56964b252ebf9ae
Quelldatensatz
uspto-grants-2008_02
Patentnummer
US07329756B2

Verknüpfte Notizen

Wird geladen…