Preparation method of lacidipine impurity B

Abstract

The invention relates to the technical field of pharmacy, and particularly discloses a preparation method of a lacidipine impurity B. The preparation method comprises the following steps: step 1), adding lacidipine into a solvent, and stirring until lacidipine is dissolved to obtain a prepared solution; step 2) slowly adding DDQ into the prepared solution at the speed of 1.0-3.0 g / min, stirring for more than 10 minutes at the stirring speed of 250-350 rpm at the temperature of 0-50 DEG C, and then filtering to obtain an organic phase, namely a lacidipine impurity B solution, wherein the molarratio of lacidipine to DDQ is 1: 1-3; and step 3) washing the lacidipine impurity B solution with a weak base aqueous solution, washing with a saturated sodium chloride aqueous solution, and spin-drying to obtain the yellow solid lacidipine impurity B. The method has the characteristics of short reaction time, simple preparation process and suitability for industrial production, and the prepared lacidipine impurity B has the advantages of high purity and good properties.

Description

technical field [0001] The application relates to the technical field of pharmacy, more specifically, it relates to a preparation method of lacidipine impurity B. Background technique [0002] Lacidipine is a lipophilic dihydropyridine calcium antagonist, commonly used in the treatment of hypertension and atherosclerosis, and has good antioxidant and vascular selectivity. Currently, lacidipine is in the form of tablets Sold around the world, it is an effective and well-tolerated drug. However, during the production process of the drug, a variety of lacidipine impurities will be produced, which are recorded as lacidipine impurity A in the European Pharmacopoeia. Cidipine impurity B, lacidipine impurity C, in the drug control testing standards, a separate control test for impurity A and impurity B is required to analyze and identify the drug quality of lacidipine. [0003] Wherein the preparation of impurity B usually exists at the same time of multiple impurities, it is diff...

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Problems solved by technology

[0003] Wherein the preparation of impurity B usually exists at the same time of multiple impurities, it is difficult to obtain a single impurity B, and the conversion rate is low. For preparation, it takes about 12 hours at room temperature to convert into the corresponding aromatized product by introducing air and irradiating with visible light. This method uses non-metal as catalyst and oxygen as oxidant. Although the conversion rate is high, but The reaction rate is slow, and a silica gel column is required to separate and purify a special catalyst, which has certain limitations in actual industrial production. There is also the use of nickel as a catalyst for preparation. Lacidipine is dissolved in an acidic aqueous solution, and nickel is used as a catalyst. Catalyst, under the oxidation of oxygen, the lacidipine impurity B can be obtained at room temperature for about 6 hours. This method has a high conversion rate and few by-products, but the catalyst is expensive and difficult to apply to industrial production

[0004] Therefore, for the above-mentioned related technologies, the inventors believe that the cost of preparing lacidipine impurity B is high and the reaction speed is slow, which needs to be further improved

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