公开(公告)号：KR100786371B1

公开(公告)日：2007-12-17

申请号：KR1020060123826

申请日：2006-12-07

Applicant: 한국화학연구원

Inventor： 최일영 ,  임희종 ,  유옥종 ,  정명희

IPC: C07D491/04

Abstract: A method for preparing galantamine is provided to synthesize the highly pure galantamine, known to show the excellent dementia treating effect, with high yield. A method for preparing galantamine comprises the steps of: (a) after reacting an oxazolidinone derivative represented by the formula(2) with an aromatic halide derivative represented by the formula(3), removing a hydroxy protection group from the product to prepare a phenol derivative represented by the formula(4b)(wherein X is a halogen atom, and Pro is a hydroxy protection group); (b) subjecting the compound of the formula(4b) in the presence of an oxidizer to an oxidative coupling reaction to prepare a spiro benzo azepine derivative represented by the formula(5); (c) reacting the compound of the formula(5) with morpholine using a Pd catalyst to prepare a stereoselective hydrofuran derivative represented by the formula(6); (d) converting C-6 hydroxy group of the compound of the formula(6) into a hydrogen atom to prepare a compound represented by the formula(7b); (e) reducing C-10 ketone of the compound of the formula(7b) to prepare a compound represented by the formula(8); (f) after hydrolyzing the compound of the formula(8) under the base condition to open an oxazolidinone ring, subjecting the product to an N-methylation reaction to prepare a compound represented by the formula(9b); (g) oxidizing the compound of the formula(9b) to prepare a compound represented by the formula(10); (h) after converting an aldehyde group of the compound of the formula(1) into oxime, dehydrating the product to prepare a compound represented by the formula(11); and (i) reducing C-6 ketone of the compound of the formula(11) and eliminating C-10 carbonitrile of the compound to prepare the galantamine represented by the formula(1).

Abstract translation: 提供一种制备加兰他敏的方法，以合成具有优异痴呆治疗效果的高纯度加兰他敏，产率高。 制备加兰他敏的方法包括以下步骤：（a）使由式（2）表示的恶唑烷酮衍生物与由式（3）表示的芳族卤化物衍生物反应后，从产物中除去羟基保护基以制备苯酚 衍生物（4b）（其中X是卤素原子，Pro是羟基保护基团）; （b）在氧化剂存在下将式（4b）化合物进行氧化偶联反应，制备由式（5）表示的螺苯并吖庚因衍生物; （c）使用Pd催化剂使式（5）的化合物与吗啉反应，制备由式（6）表示的立体选择性氢呋喃衍生物; （d）将式（6）化合物的C-6羟基转化为氢原子，制备式（7b）表示的化合物。 （e）还原式（7b）化合物的C-10酮以制备由式（8）表示的化合物; （f）在碱性条件下水解式（8）化合物以打开恶唑烷酮环后，使产物进行N-甲基化反应以制备式（9b）表示的化合物; （g）氧化式（9b）化合物以制备由式（10）表示的化合物; （h）将式（1）化合物的醛基转化为肟后，使产物脱水，制备式（11）表示的化合物; 和（i）还原式（11）化合物的C-6酮并除去该化合物的C-10腈，以制备由式（1）表示的加兰他敏。