Preparation method of N-ethyl-3-phenylpropylamine

Abstract

The invention relates to a preparation method of N-ethyl-3-phenylpropylamine, and belongs to a preparation method of a compound. The preparation method comprises the following steps: dropwise adding 3-hydrocinnamaldehyde into an alcohol solution of ethylamine hydrochloride to carry out reaction under protection of inert gas; putting metal borohydride into a reaction system to carry out reduction reaction after a reaction terminal is reached; controlling a temperature to -20 to 15 DEG C; slowly adding a quenching solution into the reaction system to stop reaction, and simultaneously hydrolyzingthe generated organic boride; carrying out separation and purification on the generated target compound N-ethyl-3-phenylpropylamine or corresponding salt of the N-ethyl-3-phenylpropylamine. The preparation method disclosed by the invention has the advantages that production of relevant tertiary amine and quaternary ammonium salt side-products is avoided, an influence of the reaction on an environment is reduced, and the method has the environmental protection advantage; the operation is safe, simple and convenient, a requirement on equipment and operation personnel is low; energy consumptionis little, the security is high, and the the method is suitable for industrialization; the yield is high, and the post-processing is simple and feasible.

Description

technical field [0001] The present invention belongs to a preparation method of a compound, and specifically refers to a cheap, mild, efficient and industrialized preparation method of N-ethyl-3-phenylpropylamine (Formula I). Background technique [0002] Alverine citrate is a highly selective calcium ion channel modulator developed by British Norgine company. First launched in the UK in 1996, it is mainly used for the treatment of irritable bowel syndrome, intestinal spasm, abdominal pain and pain caused by diverticular disease, biliary tract spasm, and spasmodic pain caused by urinary tract stones or infection. [0003] [0004] Compound N-ethyl-3-phenylpropylamine (formula I) is an important intermediate of synthetic alverine citrate (shown in Scheme 1, Ts=p-toluenesulfonyl, Ms=methylsulfonyl, Tf=trifluoro methylsulfonyl). [0005] [0006] At present, to the synthesis of compound N-ethyl-3-phenylpropylamine, mainly contain following three kinds of approaches: ...

AI Technical Summary

Problems solved by technology

[0012] (1) The reaction conditions are harsh, requiring high equipment, high energy consumption, and serious pollution. For example, using corrosive reagents such as concentrated sulfuric acid or acid chloride, it needs to be heated to 100°C or 115°C for reaction, which is not conducive to industrial production. , is also not conducive to energy saving and environmental protection; (such as documents 1-4 and 6)

[0013] (2) The reduction catalyst used in some methods is a rare metal Ru catalyst, which is expensive and not commercially available. It needs to be specially made, and it needs to be matched with a more expensive reducing agent silicon hydride to obtain satisfactory results (document 5)

[0014] (3) The reducing agent used in some methods is LiAlH, which is very sensitive to the environment and highly flammable. 4 , the reagent reacts violently, is difficult to control in use and operation, has high requirements on equipment, reaction conditions and operator level, and has fire hazards (Documents 3 and 4)

[0015] (4) Some methods have more main by-products and complex components, which are not conducive to the separation and purification of subsequent target compounds (Documents 1, 2 and 7)

[0016] (5) the yield of individual method is also relatively low (only 42%), unsatisfactory (document 6)

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