- Method for continuously synthesizing metoprolol and salts thereof
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The invention discloses a method for continuously synthesizing metoram, which comprises the following steps: (1) carrying out vacuum rectification on a 1-(2, 3-epoxypropoxy)-4-(2-methoxyethyl)benzene raw material to obtain a pure product with the purity of more than 99%, and preparing the pure product into an ethanol solution; (2) uniformly mixing the ethanol solution obtained in the step (1) with isopropylamine, feeding the mixture into a pipeline reactor, and reacting to obtain a metoprolol reaction solution; and (3) depressurizing the reaction liquid, and recovering isopropylamine in a rectifying tower, wherein the tower bottom liquid contains high-purity metoprolol. The purity of the raw materials reaches 99% or above through the rectification step, and colored impurities are also removed; when metoprolol is synthesized, a rapid reaction method of large excess of isopropylamine in the pipeline reactor is adopted, so that secondary condensation side reactions are obviously reduced, and the purity of metoprolol reaches 98% or above; and after metoprolol is salified with succinic acid, a crude drug finished product with the purity larger than 99.5% can be obtained through crystallization. The method is high in yield, low in cost and easy to operate, and is an environment-friendly process route capable of realizing industrial production.
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Paragraph 0032-0047
(2021/04/14)
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- Method for preparing metoprolol succinate
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The invention relates to a method for preparing high-purity metoprolol succinate, which adopts a single solvent system to prepare the metoprolol succinate in a reverse dropping mode. The method is simple and convenient to operate, stable in process, high in salifying yield and purity, low in process cost, and has good practical value. A single conventional solvent is adopted, so that post-treatment and solvent recovery are facilitated, and the method is environment-friendly.
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Paragraph 0036-0068
(2020/09/16)
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- Method for preparing metoprolol salt
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The invention relates to a method for preparing a metoprolol salt which is simple to operate, high in yield, good in quality, low in cost and good in environmental-friendliness. According to the method provided by the invention, an acetone/water mixed solvent system is adopted, and an adverse dropping mode, that is, a mode that metoprolol is dropped into an organic acid solution, is adopted, so that the organic acid can be sufficiently dissolved, and a reaction can be sufficiently implemented, the reaction time can be greatly shortened, and the reaction conversion rate and the yield can be increased. The operation procedures are simplified, the time is shortened, the cost is lowered, and moreover, the quality of a product is greatly improved.
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Paragraph 0054; 0055
(2017/05/12)
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- Succinic acid δ S-metoprolol of the crystal and its preparation method and application
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The invention discloses a crystal form delta of metoprolol succinate. The crystal form comprises the following characteristic peaks shown in an X-ray powder diffraction pattern when the reflection angle is 2theta: 3.98+/-0.1, 7.95+/-0.1, 10.92+/-0.1, 12.28+/-0.1, 14.66+/-0.1, 16.02+/-0.1, 18.39+/-0.1, 19.77+/-0.1 and 20.99+/-0.1. The crystal form is good in stability and slow in dissolving rate. The invention also provides a preparation method and application of the crystal form. The method for preparing the crystal form delta of metoprolol succinate has the characteristics of high repeatability and strong operationality. The crystal form delta of metoprolol succinate is applicable to prepare pharmaceutical compositions and has important application meaning on preparation of medicines for treating hypertension.
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Paragraph 0034; 0035
(2016/10/17)
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- SYNTHESIS AND PREPARATIONS OF METOPROLOL AND ITS SALTS
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The invention relates to an improved process for preparing metoprolol and its salts.
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Page/Page column 4
(2009/10/06)
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- PROCESS FOR MANUFACTURE OF METOPROLOL AND SALTS THEREOF
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Metoprolol manufacturing process with optimized reaction temperatures and reactant molar ratios, to avoid the manufacture of excessive epoxide intermediates, thus avoiding the need for purification of epoxide intermediates, thus achieving higher yields and higher-purity product than that seen in the prior art teachings.
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- Metoprolol manufacturing process
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Metoprolol manufacturing process with optimized reaction temperatures and reactant molar ratios, to avoid the manufacture of excessive epoxide intermediates, thus avoiding the need for purification of epoxide intermediates, thus achieving higher yields and higher-purity product than that seen in the prior art teachings.
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Page/Page column 3
(2010/02/11)
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