methyl 4-(2-chlorocarbonylethyl)piperidin-1-carboxylate | 179233-07-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: methyl 4-(2-chlorocarbonylethyl)piperidin-1-carboxylate
• 英文别名: 3-[N-(methoxycarbonyl)-piperidin4-yl]proprionyl chloride；methyl 4-(3-chloro-3-oxopropyl)piperidine-1-carboxylate
• CAS: 179233-07-9
• 化学式: C₁₀H₁₆ClNO₃
• 分子量: 233.695
• InChiKey: URSQIBXGYZZHMH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 4-(2-chlorocarbonylethyl)piperidin-1-carboxylate 在 三氯化铝 、 碘代三甲硅烷 作用下， 以 氯仿 、 1,2-二氯乙烷 为溶剂， 反应 19.5h， 生成 1-(2-acetyl-2,3,4,5-tetrahydro-1H-benzo[c]azepin-8-yl)-3-piperidin-4-yl-propan-1-one
  参考文献：
  名称：

  Regioselective Friedel–Crafts acylation of 2,3,4,5-tetrahydro-1H-2-benzazepine and related nitrogen heterocycles

  摘要：

  It is revealed that NH-protected 2,3,4,5-tetrahydro-1H-2-benzazepine 4 is acylated on C-8 with greater than 95% regioselectivity. This regioselectivity has been applied to the synthesis of 3-(1-benzylpiperidin-4-yl)-1-(2,3,4,5-tetrahydro-1H-2-benzazepin-8-yl)propan-1-one 3a, an inhibitor of acetylcholinesterase (AChE). The regioselectivities of the acylation of the following nitrogen heterocycles have also been studied: 4-formyl-2,3,4,5-tetrahydro-1,4-benzoxazepine 6, 2,3,4,5-tetrahydro-1H-2-benzazepin-3-one 7, 2,3,4,5-tetrahydro-1H-3-benzazepin-2-one 8, 7,11b,12,13-tetrahydro-5H-isoindolo[2,1-b][2] benzazepin-7-one 9 and 6,7,9,13b-tetrahydro-5H-isoindolo[1,2-a][2]benzazepin-9-one 10. A molecular orbital (MO) calculation on the Lewis acid coordinated substrates has been used for predicting regioselectivity.

  DOI：

  10.1039/p19940002993
• 作为产物：
  描述：

  3-[1-(acetyl)-4-piperidinyl]propionic acid 在 盐酸 、 sodium hydroxide 、 氯化亚砜 作用下， 反应 11.5h， 生成 methyl 4-(2-chlorocarbonylethyl)piperidin-1-carboxylate
  参考文献：
  名称：

  Regioselective Friedel–Crafts acylation of 2,3,4,5-tetrahydro-1H-2-benzazepine and related nitrogen heterocycles

  摘要：

  It is revealed that NH-protected 2,3,4,5-tetrahydro-1H-2-benzazepine 4 is acylated on C-8 with greater than 95% regioselectivity. This regioselectivity has been applied to the synthesis of 3-(1-benzylpiperidin-4-yl)-1-(2,3,4,5-tetrahydro-1H-2-benzazepin-8-yl)propan-1-one 3a, an inhibitor of acetylcholinesterase (AChE). The regioselectivities of the acylation of the following nitrogen heterocycles have also been studied: 4-formyl-2,3,4,5-tetrahydro-1,4-benzoxazepine 6, 2,3,4,5-tetrahydro-1H-2-benzazepin-3-one 7, 2,3,4,5-tetrahydro-1H-3-benzazepin-2-one 8, 7,11b,12,13-tetrahydro-5H-isoindolo[2,1-b][2] benzazepin-7-one 9 and 6,7,9,13b-tetrahydro-5H-isoindolo[1,2-a][2]benzazepin-9-one 10. A molecular orbital (MO) calculation on the Lewis acid coordinated substrates has been used for predicting regioselectivity.

  DOI：

  10.1039/p19940002993

文献信息

• Process for the preparation of donepezil
  申请人：CHEMAGIS LTD

  公开号：US20040048893A1

  公开（公告）日：2004-03-11

  The invention provides a process for the preparation of a compound of the formula 6 comprising the hydrolysis and decarboxylation of a compound of the formula 5 according to the reaction: 1 wherein R and R 2 independently a C 1 -C 4 alkyl group or an aralkyl group.

  该发明提供了一种配方6的化合物制备过程，包括根据反应：1对配方5的化合物进行水解和脱羧，其中R和R2分别是C1-C4烷基或芳基烷基。
• Novel Process for Production of Highly Pure Polymorph (I) Donepezil Hydrochloride
  申请人：Neu Jozsef

  公开号：US20080306271A1

  公开（公告）日：2008-12-11

  The present invention provides a novel, industrially realizable and economically preferable process for production of highly pure 1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methyl piperidine hydrochloride, i.e., donepezil hydrochloride shown in the following reaction scheme, in Polymorph (I) morphological crystal form. (I) In one of the key steps of the process, during the hydrogenation 5,6-dimethoxy 2-(pyridine-4-yhnethylene)indan- 1 -one hydrochloride is saturated using Pd carbon to get 4-[(5,6-dimethoxy- 1 -indanon)-2-yl]-methyl piperidine at more than 97% HPLC purity. In the crystallization step donepezil-hydrochloride is crystallized from an aqueous alcoholic solvent to get Polymorph (I) in at least 99.95% HPLC purity.

  本发明提供了一种新颖的、可在工业上实现的、经济上优选的过程，用于生产高纯度的1-苄基-4-[(5,6-二甲氧基-1-吲哚酮)-2-基]甲基哌啶盐酸盐，即多奈哌齐盐酸盐，以Polymorph (I)形态晶体形式呈现在以下反应方案中。在该过程的关键步骤之一中，在氢化过程中，使用Pd碳饱和5,6-二甲氧基2-(吡啶-4-基亚乙烯基)吲哚-1-酮盐酸盐以获得在97%以上的HPLC纯度下的4-[(5,6-二甲氧基-1-吲哚酮)-2-基]甲基哌啶。在结晶步骤中，多奈哌齐盐酸盐从水醇溶剂中结晶出来，以至少99.95%的HPLC纯度得到Polymorph (I)。
• Processes for Preparing Donepezil
  申请人：Kharatkar Raju Mahadev

  公开号：US20100105916A1

  公开（公告）日：2010-04-29

  A process for preparing highly pure donepezil, particularly donepezil hydrochloride, is provided comprising hydrogenating compound 1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-ylidene]methyl-piperidine or its hydrochloride salt with a noble metal catalyst or a derivative thereof, in the presence of at least one additive, wherein the additive contains at least one heteroatom, e.g., a sulfur, phosphorous, or nitrogen heteroatom.

  提供了一种制备高纯度多奈哌齐（尤其是盐酸多奈哌齐）的方法，包括在至少一种添加剂的存在下，使用贵金属催化剂或其衍生物对化合物1-苄基-4-[(5,6-二甲氧基-1-茚酮)-2-基亚甲基]-哌啶或其盐酸盐进行氢化反应，其中该添加剂包含至少一个杂原子，例如硫、磷或氮杂原子。
• Processes and intermediates for preparing 5,
  申请人：Pfizer Inc.

  公开号：US05916902A1

  公开（公告）日：1999-06-29

  This invention relates to a process for preparing the compound having the formula ##STR1## which comprises i) heating the compound of formula ##STR2## wherein R.sup.3 is R.sup.4 or benzyl and R.sup.4 is R.sup.5 C(.dbd.O), R.sup.5 C(.dbd.O) or R.sup.5 SO.sub.2 wherein R.sup.5 is (C.sub.1 -C.sub.6)alkyl or (C.sub.6 -C.sub.10)aryl(C.sub.1 -C.sub.6)alkyl; at an elevated temperature in the presence of a base with the proviso that when R.sup.3 in the resultant product is R.sup.4 said product is ii) further treated with an aqueous mineral acid at an elevated temperature followed by iii) treatment of the product of ii) with a) a benzylating agent in the presence of a base or b) benzaldohyde in the presence of a reducing agent and an acid.

  本发明涉及一种制备具有以下式子的化合物的方法：##STR1## 其中，i）在碱的存在下在高温下加热具有以下式子的化合物：##STR2## 其中，R.sup.3为R.sup.4或苄基，R.sup.4为R.sup.5 C(.dbd.O)、R.sup.5 C(.dbd.O)或R.sup.5 SO.sub.2，R.sup.5为（C.sub.1-C.sub.6）烷基或（C.sub.6-C.sub.10）芳基（C.sub.1-C.sub.6）烷基；但是当所得产物中R.sup.3为R.sup.4时，该产物需要进行ii）进一步处理，即在高温下用水矿酸处理，然后再用a）苄基化试剂在碱的存在下处理或b）苯甲醛在还原剂和酸的存在下处理。
• Process for the Preparation of Highly Pure Donepezil
  申请人：Aggarwal Ashvin Kumar

  公开号：US20100113793A1

  公开（公告）日：2010-05-06

  The present invention relates to the preparation of highly pure donepezil of formula I or salt thereof, by hydrogenating indanonylidenyl compound of formula II, using platinum catalysts.

  本发明涉及使用铂催化剂，通过氢化II式的茚醇亚胺化合物，制备高纯度I式多奈哌齐或其盐。