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

関与物質

反応手順

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).

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