泊沙康唑
化学
杂质
再结晶(地质)
抗真菌
抗真菌药
过程开发
组合化学
过程(计算)
SN2反应
工艺工程
有机化学
微生物学
操作系统
工程类
古生物学
生物
两性霉素B
计算机科学
作者
Wanfang Li,Bin Wang,Shouxiang Jiang,Qi‐Long Zhang,Kai Fu,Gengxiu Zheng
标识
DOI:10.1016/j.tetlet.2023.154574
摘要
A practical synthesis method for the large-scale preparation of Posaconazole is developed. The key intermediate 7 was obtained initially with substantial amounts (∼11.70%) of process impurity A when performed the SN2 reaction. Based on the structure elucidation and careful investigation, it was verified that the formation of impurity A was closely related to the presence of oxygen. Hence, the content of A was below 0.1% after displacing the oxygen, which fundamentally avoided the recrystallization of 7. Furthermore, the efficient removal of palladium (less than 10 ppm) was achieved by the low cost and convenient operation of mercapto silica after the debenzylation of 7, which ensured the high quality of Posaconazole. Finally, the optimized process was successfully implemented (15 kg) and provided Posaconazole (>99.90%) with an overall yield of 82%. This work provides a reference for the manufacture of the antibacterial drug Posaconazole.
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