171482-05-6Relevant articles and documents
Preparation method of aprepitant key intermediate
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Paragraph 0046-0065, (2021/06/12)
The invention provides a preparation method of an aprepitant key intermediate, which comprises the following steps: S1) carrying out a Grignard reaction on (2R)-4-benzyl-2-[(1R)-1-[3, 5-bis(trifluoromethyl) phenyl] ethyoxyl] morpholine-3-ketone and 4-fluo
Intermediates for preparing aprepitant, and preparation method and application thereof
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Paragraph 0127-0161, (2020/02/20)
The invention belongs to the technical field of compounds and synthesis thereof, and provides intermediates for preparing aprepitant, and a preparation method and an application thereof. The inventionprovides the aprepitant preparation intermediate represented by formula I and the aprepitant preparation intermediate represented by formula II. The aprepitant is prepared from the two intermediatesthrough condensation and reduction reactions. Compared with existing methods for preparing aprepitant, the method of the invention has the advantages of avoiding of the disadvantages of complex reaction process, multiple transition states and multiple byproducts in the intermediate preparation process and the disadvantage of complex quality control, simple synthesis process of aprepitant, enhancement of the safety and process controllability of industrial production, high yield, no pollution, easily available raw materials, simplicity in industrial operation, low energy consumption, low cost,safety and environment friendliness, and is suitable for industrial application.
High-purity aprepitant preparation method
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Paragraph 0020-0025, (2020/01/25)
The invention discloses a high-purity aprepitant preparation method, which specifically comprises: 1, carrying out a reaction on (R)-4-benzyl-2-((R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)morpholine-3-one, tetrahydrofuran and 4-fluorophenyl magnesium bromide, carrying out a reaction on the reaction solution, a toluenesulfonic acid monohydrate and a catalyst, leaching with methanol, adding othersubstances, and adding hydrochloric acid, 4-methyl-2-pentanone, ethanol and n-heptane into the organic layer of the product to obtain (2R,3S)-2-((R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(4-fluorobenzene)morpholine hydrochloride; and 2, dissolving the product obtained in the step 1 in an alcohol solvent and a reverse solvent, heating until the solution is clear, cooling, and crystallizing toobtain the finished product. According to the invention, the preparation method is easy to control, the purity of the prepared (2R,3S)-2-((R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(4-fluorobenzene) morpholine hydrochloride can reach more than 99.5%, the defluorination impurity content is lower than 0.05%, and the purity of the prepared finished product can reach more than 99.9%.