Preparation method of 3, 5-bis (trifluoromethyl) acetophenone

Abstract

The invention provides a preparation method of 3, 5-bis (trifluoromethyl) acetophenone. 3, 5-bis (trifluoromethyl) acetophenone is synthesized by using 3, 5-bis (trifluoromethyl) bromobenzene as a rawmaterial. The preparation method comprises the following steps: under a reaction temperature, selectively mixing either N-methoxy-N-methylacetamide or N-methoxy-N-methylformamide with 3, 5-bis (trifluoromethyl) bromobenzene and n-butyl lithium, and carrying out a stirring reaction under a reaction solvent condition at a reaction temperature of -70 to -90 DEG C; and executing a post-processing step, namely, heating to room temperature, extraction and washing, drying and evaporating to remove the residual solvent, and performing column chromatography separation to obtain 3, 5-bis (trifluoromethyl) acetophenone. According to the invention, cheap 3, 5-bis (trifluoromethyl) bromobenzene as a raw material directly reacts with N-methoxy-N-methylacetamide to obtain the high-yield 3, 5-bis (trifluoromethyl) acetophenone, the method is simple in reaction steps, easy to control and suitable for industrial production, so that a more valuable synthesis route is provided for preparation of aprepitant, good social benefits and economic benefits can be brought, and the economic value potential is relatively large.

Description

technical field [0001] The invention relates to the technical field of organic compound synthesis and pharmacy, and more specifically, relates to a preparation method of 3,5-bistrifluoromethylacetophenone for synthesizing aprepitant. Background technique [0002] Aprepitant is the first neurokinin-1 (NK-1) receptor blocker approved by the US FDA in 2003. It is mainly used to prevent or treat nausea and vomiting caused by chemotherapy. Pyritant is a drug that blocks the action of substance P (a neuropeptide widely distributed in fine nerve fibers) by combining with NK-1 receptors (mainly present in the central nervous system and its periphery), and can pass through the blood The brain barrier occupies the NK-1 receptors in the brain, has selectivity and high affinity for NK-1 receptors, but has low affinity for NK-2 and NK-3 receptors; at the same time, it has high affinity for NK-1 receptors; Targets of other drugs used to treat chemotherapy-induced nausea and vomiting (suc...

AI Technical Summary

Problems solved by technology

[0009] The method has high cost of raw materials, long reaction steps, low yield, great environmental pollution, and is not suitable for expanding production

[0010] In summary, the prior art 3,5-bistrifluoromethylacetophenone synthesis method or steps are complicated, or the yield is low, or the cost is high, so a simple and efficient 3,5-bistrifluoromethyl acetophenone is needed The synthetic method of methyl acetophenone

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