144689-93-0Relevant articles and documents
Synthetic method for preparing olmesartan medoxomil intermediate through continuous flow
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Paragraph 0036-0044, (2021/09/04)
The invention discloses a synthetic method for preparing an olmesartan medoxomil intermediate through continuous flow, which belongs to the technical field of drug synthesis. The method comprises the following steps: step (1), dissolving a compound 2-propyl-4,5-imidazole dicarboxylic acid ethyl ester I in an organic solvent to form a reaction phase A; step (2), taking a commercially purchased methyl magnesium chloride solution as a reaction phase B; step (3), pumping the reaction phase A and the reaction phase B into a mixer by using a plunger pump at a certain flow rate, then feeding the mixture into a reactor, retaining for a certain time, quenching by using an acid water phase C, feeding the mixture into an oil-water continuous liquid separator, separating liquid to obtain an organic solution of a compound as shown in a formula II, desolventizing, and recrystallizing to obtain the compound as shown in the formula II. The technical problems of low purity and high cost in the existing preparation process are solved, the product is high in purity and few in impurities, the content of the key impurity A, the key impurity B and the key impurity C can be controlled to be 0.1% or below, the raw materials are cheap and easy to obtain, the reaction condition is mild, operation is easy and convenient, the synthesis efficiency is high, and the method is suitable for industrial production. A novel continuous flow path is provided for preparing the olmesartan medoxomil and the intermediate.
4-(1-hydroxyl-1-methylethyl)-2-propylimidazole-5-carboxylic ethyl ester monohydrate
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Paragraph 0084; 0085; 0086; 0087, (2019/01/14)
The invention relates to a 4-(1-hydroxyl-1-methylethyl)-2-propylimidazole-5-carboxylic ethyl ester monohydrate (namely a compound shown in a formula 2) and a preparation method and application thereof. The compound can be obtained by crystallization in organic solvents, such as an acetone and water mixed solvent, in mutual solubility with water. The 4-(1-hydroxyl-1-methylethyl)-2-propylimidazole-5-carboxylic ethyl ester monohydrate is high in purity and yield, and subsequent olmesartan medoxomil synthesis is benefited.
Amazingel medoxomill intermediate 4 - (1-hydroxy-1-methyl ethyl) - 2-propyl-imidazol-5-carboxylic acid ethyl ester preparation method and application
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Paragraph 0070-0072, (2017/05/12)
The invention provides a preparation method of ethyl 4-(1-hydroxy-1-methylethyl)-2-propylimidazolyl-5-carboxylate (1). The method accurately controls the reaction material ratio, solvent composition, solvent consumption, reaction temperature, reaction time and other technological parameters, and obviously lowers the content of the impurity compound disclosed as Formula 3, thereby obtaining the high-purity olmesartan medoxomil. The invention also provides application of the compound disclosed as Formula 3 as a quality control standard substance in preparing the ethyl 4-(1-hydroxy-1-methylethyl)-2-propylimidazolyl-5-carboxylate (1).