氢溴酸达非那新的合成

Synthesis of Darifenacin Hydrobromide

邻溴苯酚经O-烷基化、环合得2,3-二氢苯并呋喃,再经Friedel-Crafts酰化、Wilgerodt反应、水解、酯化、还原和取代反应得到5-(2-溴乙基)-2,3-二氢苯并呋喃,然后与3-(S)-(?)-(1-氨甲酰基-1,1-二苯基甲基)吡咯烷反应、成盐得到氢溴酸达非那新,总收率约8%。

Darifenacin hydrobromide was synthesized from o-bromophenol by O-alkylation,cyclization,Friedel-Crafts reaction,Wilgerodt reaction,hydrolysis,esterification,reduction and bromo substitution to give 5-(2-bromoethyl)-2,3-dihydrobenzofuran,which was subjected to condensation with 3-(S)-(-)-(1-carbomoyl-1,1diphenylmethyl)pyrrolidine and then salt formation with an overall yield of about 8%.