索菲那新的合成

Synthesis of Solifenacin

以β-苯乙胺为原料,经酰化生成N-苯乙基苯甲酰胺,再与多聚磷酸(PPA)反应生成1-苯基-3,4-二氢异喹啉,经还原生成1-苯基-1,2,3,4-四氢异喹啉,拆分得到(S)-1-苯基-1,2,3,4-四氢异喹啉,最后经酰化、酯化得到最终产物索菲那新(1-(S)-苯基-1,2,3,4-四氢异喹啉-2-甲酸-3-(R)-奎宁环酯),反应总收率21.79%,产物结构由1 H-NMR光谱表征.该工艺制备索菲那新的方法简单,原料便宜,后处理容易,适用于工业化生产.

The β-phenylethylamine was used as the starting material to synthesize Solifenacin （1-（s）- Phenyl-1, 2, 3, 4-tetrahydro-isoquinoline-2-carboxylic acid 3-（R）-quinuclidinyl ester） by six steps. acetylation with benzoyl chloride, cyclization with PPA, reduction with KBH4, resolution with D-tar- taric acid ,acylation with ethyl chloroformate and esterification with （R）-（-）-3-Quinuclidinol. The to- tal yield is 21. 79%, and the structure of solifenacin was identified by 1H-NMR spectroscopy. The method of preparation is much easier to perform and Work up with cheaper starting materials and suit- able for industrialization.