1-phenyl-1, 2, 3, 4-tetrahydroisoquinoline preparation method

Abstract

The invention provides a 1-phenyl-1, 2, 3, 4-tetrahydroisoquinoline preparation method. The 1-phenyl-1, 2, 3, 4-tetrahydroisoquinoline preparation method comprises the following steps of: mixing benzoyl chloride or benzoic acid, phenethylamine and alkali metal hydroxide with water, and reacting to obtain N-(2-phenethyl) benzamide; then mixing the N-(2-phenethyl) benzamide with phosphorus pentoxide, chloride phosphorus and a benzene solvent, heating and reacting to obtain 1-phenyl-3, 4-dihydro-isoquinoline; and further mixing the 1-phenyl-3, 4-dihydro-isoquinoline with a first alcohol solvent and hydroboron, and reacting to obtain the product. Compared with the prior art, the 1-phenyl-1, 2, 3, 4-tetrahydroisoquinoline preparation method has the advantages that firstly, no organic solvents are added, the product N-(2-phenethyl) benzamide is insoluble in an aqueous solution, and therefore, the steps of skimming and the like are avoided in the after-treatment process, and the after-treatment operation is simplified; secondarily, as the organic solvents are not added, the cost is reduced, and the pollution to environments is avoided; and thirdly, as the phosphorus pentoxide and the chloride phosphorus are subjected to oxidization cyclization reaction, polyphosphoric acids are prevented from being heated and decomposed to generate hypertoxic phosphorus oxide exhaust gas.

Description

technical field [0001] The invention belongs to the technical field of synthesis and preparation of organic compounds, in particular to a preparation method of 1-phenyl-1,2,3,4-tetrahydroisoquinoline. Background technique [0002] Solifenacin, the chemical name is 1-phenyl-1,2,3,4-tetrahydro-2-isoquinolinecarboxylic acid (1R,3R′)-quinuclidinyl ester. It has been reported that a series of quinucidine derivatives including solifenacin or its salts have no effect on muscarine M 3 The receptor has excellent selective antagonism and is useful in urological disorders such as neurogenic urinary frequency, neurogenic bladder, nocturia, unstable bladder, bladder contractures, and chronic cystitis, as well as in respiratory disorders such as chronic obstructive pulmonary disease , chronic bronchitis, asthma and rhinitis) preventive or therapeutic agents. Among them, solifenacin is a urinary system antispasmodic drug, is M 3 Selective antagonists of receptors, usually used to treat ...

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Problems solved by technology

[0006] However, existing literature such as the synthesis of solifenacin (Journal of Wuhan University of Technology, 2012, 36(5): 1095-1907) and the synthesis of solifenacin succinate (Chinese Journal of Pharmaceutical Industry, 2012, 43(1): The synthesis of the amide intermediate in the first step in 1-4) uses phenylethylamine and benzoyl chloride to react in an organic solvent, but after the reaction is completed, it needs to go through steps such as liquid separation, pickling, water washing and drying, and post-processing operations The steps are cumbersome, resulting in low reaction yields, and organic solvents also have an impact on the environment

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