摘要
探讨了左旋泮托拉唑钠、镁的合成。以麦芽酚(2-甲基-3-羟基-4-吡喃酮)为起始原料,经过甲基化、氨化、氯化、氧化、甲氧基化、重排、水解、氯化反应合成得到2-氯甲基-3,4-二甲氧基吡啶盐酸盐;以扑热息痛(对乙酰氨基酚)为原料经过醚化、硝化、还原、环合反应合成5-二氟甲氧基-2-巯基-1H-苯并咪唑;二者缩合制得5-二氟甲氧基-2-{[(3,4-二甲氧基-2-吡啶基)甲基]硫}-1H-苯并咪唑;以D-(-)-酒石酸二乙酯为手性试剂,过氧化异丙苯为氧化剂,不对称氧化制得S-(-)-5-二氟甲氧基-2-[(3,4-二甲氧基-2-吡啶基)甲基]亚硫酰基-1H-苯并咪唑;然后与氢氧化钠、氯化镁成盐制得左旋泮托拉唑钠和左旋泮托拉唑镁。通过该法得到了目标产物左旋泮托拉唑钠和左旋泮托拉唑镁,且该合成方法操作简便。
To explore the synthesis of S- pantoprazole sodium and magnesium,maltol（ 3- hydroxy- 2- methyl- 4-pyrone） was used as row material, through a process of methylation, ammonization, chlorination, oxidation,methoxylation, rearrangement reaction, hydrolyzation, the hydrochloride form of the 2- chloromethyl- 3,4-dimethoxypyridine was obtained. Panadol（ acetaminophen） was also used as row material to obtain 5-difluoromethoxy-2- mercapto- 1H- benzimidazole by the steps of herification,nitration,deoxidization,ring- closure reaction. The pantoprazole was synthesized from those two compounds by condensation. S-（-）- 5- difluoromethoxy- 2- { [（ 3,4-dimethoxy-2-pyridinylmethyl） ]sulphinyl}-1H-benzimidazole was synthesized from（-）-diethyl D-tartrate as the chiral reagent and cumene hydroperoxide as the oxidizing agent by asymmetric oxidation. It was salified with sodium hydroxide and magnesium chloride. S-pantoprazole sodium and S-pantoprazole magnesium were made. Result showed that（ S）-（-） pantoprazole sodium and magnesium can be prepared by this simple method.
出处
《广州化工》
CAS
2016年第6期58-59,103,共3页
GuangZhou Chemical Industry
基金
湖南省怀化市科学技术局项目(2014年市级第一批6号)
湖南医药学院科研项目(2013KY02)
