Method for preparing 4-methyl-3-oxo-N-phenyl-pentanamide

Abstract

The invention relates to the preparation of a medical intermediate, particularly a method for preparing 4-methyl-3-oxo-N-phenyl valeramide. Amidation reaction is performed between isobutyryl methyl acetate and aniline, and then 4-methyl-3-oxo-N-phenyl valeramide is obtained after being processed; the charge molar ratio between isobutyryl methyl acetate and aniline is 1:0.5 to 10. The method has simple and convenient operation and high yield which is not less than 96 percent; the obtained product has fewer impurities, and the content is more than 98 percent. In addition, aniline is recycled and reused easily, residual aniline can be removed during the refining process, and the reaction time is shortened.

Description

(1) Technical field [0001] The invention relates to the preparation of pharmaceutical intermediates, in particular to a preparation method of 4-methyl-3-oxo-N-phenylpentanamide. (2) Background technology [0002] 4-Methyl-3-oxo-N-phenylpentanamide is the preparation of atorvastatin main ring 4-fluoro-α-(2-methyl-1-oxopropyl)-γ-oxo-N, The key intermediate of β-diphenylbenzenebutyramide. [0003] Patent US5,097,045 discloses the synthesis of 4-methyl-3-oxo-N-phenylpentanamide: using toluene as a reaction solvent, ethylenediamine as a catalyst, methyl isobutyrylacetate and aniline added in batches During the reaction process, the methanol generated by the reaction was continuously heated and refluxed. After the reaction, a part of the solvent was distilled off at normal pressure, and the solvent was recovered by distillation under reduced pressure at room temperature of 85 mmHg for 16 hours. After cooling, adding water to extract the organic layer, heating and adding water , ...

AI Technical Summary

Problems solved by technology

[0004] According to the study of US5,097,045, it can be found that in order to evaporate the generated methanol in time, the reaction temperature needs to be continuously increased during the process, and the raw materials and products will decompose when heated for a long time, resulting in increased impurities and poor quality in the product, with a content of 94- 95%; the yield is low, only 70-80%; the production process is unstable and the cost is high; the recovery process of the solvent toluene is complicated and cumbersome, and the recovered toluene needs to be re-distilled to a high-quality product before it can be used, and there will be residual A large amount of high-boiling waste liquid needs to be treated, which is not conducive to industrial operation and production, and also brings a certain pressure on environmental protection