A kind of purification method of n-ethyl-3-phenylpropylamine

Abstract

The invention relates to a purifying method of N-ethyl-3-phenylpropylamine, and belongs to purifying method of compounds. A N-ethyl-3-phenylpropylamine sample with the lower purity is dissolved in a water insoluble organic solvent, the organic phase is extracted for 1-5 times by a water solution with the appropriate pH value, the aqueous phase is combined, alkali or an alkaline solution is added,the pH value is conditioned, the aqueous phase is extracted by the water insoluble organic solvent, the organic phase is combined, drying and filtration are conducted, and the solvent is dried out through decompression. The purifying method has the advantages that the purifying effect is good, the result is stable and reliable, thus the higher and higher quality requirement of the pharmacy industry for the midbody can be better satisfied, and the yield is high and can be as high as 80% or above. Production and operation are safer and more convenient, and the purifying method is suitable for large-scale production.

Description

technical field [0001] The present invention belongs to a purification method of a compound, and specifically refers to a purification method of N-ethyl-3-phenylpropylamine (formula I) which is cheap, convenient, low energy consumption, high purity, high yield and suitable for industrialization. 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). Due to the application of N-ethyl-3-phenylpropylamine in the pharmaceutical...

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Problems solved by technology

[0009] 3) Only a preliminary liquid-liquid extraction method is used for preliminary purification to obtain a compound shown in formula I with lower purity without further purification (document 5, William J.Horgan, Propylamine derivatives, GB 2246778A; document 6, Poplar Dan, Zhang Yubin, Wang Lanzhou, Ji Qinggang, Synthesis of alverine citrate, China Journal of Pharmaceutical Industry, 2012, 43(3): 164-166; Literature 7, Zhang Yubin, Ji Qinggang, Wang Lanzhou, a new citron Preparation method of alverine acid, patent application number: 200910103386.8)

[0012] 1, most of the methods reported, the effect of purification is not clear (only document 1 has provided the content that the compound shown in formula I after purification can reach: 95%, but relative to the actual requirements of the quality control work in the pharmaceutical field Said, this content is obviously on the low side), most documents all do not set forth the content or the purity (document 2-7) of the compound shown in formula I after purification, have influenced the reliability of these methods use;

[0013] 2. Some documents use distillation to purify the compound shown in formula I, which has high energy consumption and low yield, which is unsatisfactory (documents 1-3, wherein the highest yield is only 63% (document 3));

[0014] 3. There are also organic solvents used in some purification methods (as solvents for extraction, precipitation and washing precipitation) that are very unstable (very easy to produce peroxides, which easily cause explosion hazards), easy to anesthetize, extremely flammable and explosive Diethyl ether has extremely high requirements on factory buildings and equipment, and it is very difficult to realize industrialization (Documents 1, 4 and 5);

[0015] 4. There are also individual methods that need to adopt special distillation devices, such as Kugelrohr steam flow device (document 3), which is not conducive to industrialization

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