(R*,R*)-7-phenyl-1-azabicyclo[4.2.0]octan-8-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂环丁烷
• 英文名称: (R*,R*)-7-phenyl-1-azabicyclo[4.2.0]octan-8-one
• 英文别名: (6S,7S)-7-phenyl-1-azabicyclo[4.2.0]octan-8-one
• 化学式: C₁₃H₁₅NO
• 分子量: 201.268
• InChiKey: BGCURPUAMJAFSI-RYUDHWBXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.16
• 重原子数：
  15.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  20.31
• 氢给体数：
  0.0
• 氢受体数：
  1.0

反应信息

• 作为反应物：
  描述：

  (R*,R*)-7-phenyl-1-azabicyclo[4.2.0]octan-8-one 在 盐酸 作用下， 以 甲醇 为溶剂， 以80%的产率得到盐酸右哌甲酯
  参考文献：
  名称：

  Changing stereoselectivity and regioselectivity in copper(i)-catalyzed 5-exo cyclization by chelation and rigidity in aminoalkyl radicals: synthesis towards diverse bioactive N-heterocycles

  摘要：

  螯合、刚性和氨基烷基前体中的碳自由基位置会干扰通常的2,4-trans 反式选择性和5-exo 模式在Cu(i)-催化的ATRC中。

  DOI：

  10.1039/c9nj05166j
• 作为产物：
  描述：

  N-(2,2,2-trichloroethylidene)prop-2-en-1-amine 在 偶氮二异丁腈 、 四甲基乙二胺 、 三正丁基氢锡 、 三乙胺 、 copper(l) chloride 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 、 甲苯 为溶剂， 生成 (R*,R*)-7-phenyl-1-azabicyclo[4.2.0]octan-8-one
  参考文献：
  名称：

  Changing stereoselectivity and regioselectivity in copper(i)-catalyzed 5-exo cyclization by chelation and rigidity in aminoalkyl radicals: synthesis towards diverse bioactive N-heterocycles

  摘要：

  螯合、刚性和氨基烷基前体中的碳自由基位置会干扰通常的2,4-trans 反式选择性和5-exo 模式在Cu(i)-催化的ATRC中。

  DOI：

  10.1039/c9nj05166j

文献信息

• [EN] IMPROVEMENTS IN OR RELATING TO ORGANIC MATERIAL<br/>[FR] AMÉLIORATIONS APPORTÉES OU SE RAPPORTANT AUX MATÉRIAUX ORGANIQUES
  申请人：UNIV LIEGE

  公开号：WO2018050546A1

  公开（公告）日：2018-03-22

  The invention provides a method for the preparation of an intermediate for use in synthesizing a lower alkyl phenidate compound of formula (I), wherein each R1 independently represents an optionally substituted aryl, heteroaryl, alkyl, cycloalkyl, alkoxy, aryloxy, acyl, carboxyl, hydroxyl, halogen, amino, nitro, sulfo or sulfhydryl group, R2 represents a hydrogen atom or a lower alkyl group, n represents an integer from 1 to 5 and m represents an integer from 1 to 3 or a pharmaceutically acceptable salt thereof; which method comprises the steps of: (a) flowing a tosylhydrazone compound of formula (IV), wherein R1, n and m are as defined above in relation to the methylphenidate of formula (I), an organic base and an organic solvent into a fluidic network; and (b) reacting the tosylhydrazone compound of formula (IV) and the base in the fluidic network under thermal and/or photochemical conditions to form a transient diazoamide compound of formula (V), wherein R1, n and m are as defined above in relation to the methylphenidate of formula (I).

  该发明提供了一种制备用于合成化合物的中间体的方法，该化合物是具有如下式(I)的较低烷基苯二酸酯化合物，其中每个R1都独立地代表一个可选择取代的芳基、杂环芳基、烷基、环烷基、烷氧基、芳氧基、酰基、羧基、羟基、卤素、氨基、硝基、磺酰基或硫氢基，R2代表氢原子或较低烷基基团，n表示1到5的整数，m表示1到3的整数或其药用可接受的盐；所述方法包括以下步骤：(a)将如下式(IV)中定义的R1、n和m与上述关于如下式(I)的甲基苯二酸酯相关的甲磺酰腙化合物、有机碱和有机溶剂导入到流体网络中；以及(b)在热和/或光化学条件下在流体网络中将如下式(IV)中定义的甲磺酰腙化合物和碱反应以形成如下式(V)的瞬时重氮酰胺化合物，其中R1、n和m如上述关于如下式(I)的甲基苯二酸酯相关的定义。
• Process for the preparation of threo-methylphenidate hydrochloride
  申请人：ISP INVESTMENTS INC.

  公开号：US20040176412A1

  公开（公告）日：2004-09-09

  The present invention provides a process for the preparation of threo-methylphenidate hydrochloride. According to a preferred embodiment, the process comprises the following steps: (a) contacting 1-(phenylglyoxylyl)piperidine arenesulfonylhydrazone of the formula 1 wherein Ar denotes an aryl group, where the aryl group may be substituted by a C 1 -C 6 alkyl, halo or nitro group; with an inorganic base in the presence of a water immiscible organic solvent and a phase transfer catalyst to obtain (R*,R*)-enriched 7-phenyl-1-azabicyclo[4.2.0]octan-8-one of the formula: 2 (b) reacting the (R*,R*)-enriched 7-phenyl-1-azabicyclo[4.2.0]octan-8-one prepared in step (a) with a solution of hydrogen chloride in methanol to obtain threo-enriched methylphenidate hydrochloride; (c) crystallizing the threo-enriched methylphenidate hydrochloride prepared in step (b) to give the desired threo-methylphenidate hydrochloride. Preferably, the threo-methylphenidate hydrochloride produced by the process of the present invention contains no more than 1% of the erythro-isomer.

  本发明提供了一种制备左旋甲基苯丙胺盐酸盐的方法。根据一个优选实施例，该方法包括以下步骤：(a)将式1中Ar代表芳基的1-(苯基甘氧基基)哌啶芳磺酰肼与一种无机碱在水不相溶有机溶剂和相转移催化剂的存在下接触，以获得(R*,R*)-富集的7-苯基-1-氮杂双环[4.2.0]辛酮的化合物：2(b)将步骤(a)中制备的(R*,R*)-富集的7-苯基-1-氮杂双环[4.2.0]辛酮与甲醇中的盐酸氢溶液反应，以获得左旋富集的甲基苯丙胺盐酸盐；(c)结晶步骤(b)中制备的左旋富集的甲基苯丙胺盐酸盐，以得到所需的左旋甲基苯丙胺盐酸盐。最好，本发明的方法生产的左旋甲基苯丙胺盐酸盐不含多于1%的对映异构体。
• Reactions of carbonyl compounds in basic solutions. Part 15. The alkaline hydrolysis of N-methyl, N-phenyl and bicyclo lactams, penicillins and N-alkyl-N-methylacetamides
  作者：Keith Bowden、Keith Bromley

  DOI：10.1039/p29900002111

  日期：——

  suggest the detailed mechanisms. All the β-lactams appear to react with rate-determining addition of hydroxide anion; while the N-alkyl γ- and δ-lactams and N-alkyl-N-methylacetamides have rate-determining ring fission of the tetrahedral adduct, assisted by water-catalysis. The reactivity of penicillin in alkaline hydrolysis has been analysed by the studies of model compounds. These show that the increased

  已经在几个温度下测量了在水中或在二甲基亚砜水溶液中一系列N-甲基，N-苯基和双环内酰胺，青霉素和N-烷基-N-甲基乙酰胺的碱水解速率系数。在底物和碱中反应都是一级反应。反应性与底物的结构有关，特别是N-取代，环大小和稠环效应。反应性以及活化参数，动力学溶剂和溶剂同位素效应均被用来表明详细的机理。所有的β-内酰胺似乎都与决定加入氢氧根阴离子的反应。而N-烷基γ-和δ-内酰胺和N-烷基-N-甲基乙酰胺具有速率决定四面体加合物的环裂变，并借助水催化。青霉素在碱性水解中的反应性已通过模型化合物的研究进行了分析。这些表明，青霉素β-内酰胺环的增加的反应性是由稠合的环结构和酰氨基侧链的直接作用引起的。
• Phenidate drug formulations having diminished abuse potential
  申请人：Celgene Corporation

  公开号：US06528530B2

  公开（公告）日：2003-03-04

  Phenidate drug formulations are provided having reduced potential for drug abuse. Dosage forms for treating Attention Deficit Disorder, Attention Deficit Hyperactivity Disorder, AIDS Dementia Complex and cognitive decline in HIV-AIDS are provided which minimize drug hypersensitivity, toxicity, side effects, euphoric effect, and drug abuse potential. Such dosage forms comprise D-threo stereoisomer of a phenidate in the substantial absence of all other stereoisomers.

  提供了具有减少滥用潜力的苯乙酸哌甲酯药物制剂。提供用于治疗注意力缺陷障碍、注意力缺陷多动障碍、艾滋病痴呆综合征和艾滋病认知衰退的剂型，这些剂型最小化了药物过敏、毒性、副作用、欣快感和滥用潜力。这些剂型包括苯乙酸哌甲酯的D-异构体，在实质上缺乏所有其他立体异构体。
• A Stereoselective Synthesis of <i>dl-threo-</i>Methylphenidate:  Preparation and Biological Evaluation of Novel Analogues
  作者：Jeffrey M. Axten、Lori Krim、Hank F. Kung、Jeffrey D. Winkler

  DOI：10.1021/jo982214t

  日期：1998.12.1