奈必洛尔关键中间体的合成新工艺  

New Synthetic Process of the Key Intermediate of Nebivolol

作　　者：程祖福 王福军 蒲通 陈恬 宋庆宝[3] CHENG Zufu;WANG Fujun;PU Tong;CHEN Tian;SONG Qingbao(Jiangsu Baju Pharmaceutical Co., Ltd., Yancheng 224555;Zhejiang Charioteer Pharmaceutical Stock Co.. Ltd., Taizhou 317321;School of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014)

机构地区：[1]江苏八巨药业有限公司,江苏盐城224555 [2]浙江车头制药股份有限公司,浙江台州317321 [3]浙江工业大学化工学院,浙江杭州310014

出　　处：《中国医药工业杂志》2018年第7期940-943,共4页Chinese Journal of Pharmaceuticals

摘　　要：本研究采用新路线合成奈必洛尔关键中间体2-氯-1-(6-氟-3,4-二氢-2H-1-苯并吡喃-2-基)乙酮。以6-氟-3,4-二氢-2H-1-苯并吡喃-2-羧酸为原料,经与氯甲酸乙酯缩合、与重氮甲烷重氮化、氯代反应"一锅法"制得目标化合物,收率85%,纯度≥99%。本工艺对产物的手性几乎没有影响,最终合成的产物与所选用的原料手性一致,手性纯度≥99.5%。本工艺已经过中试放大验证。2-Chloro- 1- （6-fluoro-3,4-dihydro-2H- 1-benzopyran-2-yl） ethan- 1 -one, the key intermcdiate of nebivolol, was synthesized by a new synthetic process. The target compound was prepared by ＂one-pot＂ method of condensation of 6-fluoro-3,4-dihydro-2H-1-benzopyran-2-carboxylic acid with ethyl chloroformate, followed by diazotization and chlorination. The yield was 85% and the purity was more than 99% with a chiral purity of 99.504. The chirality of the target product was identical to the starting material＇s. This process has been proven by pilot-scale test.

关 键 词：奈必洛尔 高血压 6-氟-3 4-二氢-2H-1-苯并吡喃-2-羧酸 重氮甲烷 中间体 

分 类 号：R972.4[医药卫生—药品] R914.5[医药卫生—药学]