N-Boc-2-methyl-6-piperidine-carboxaldehyde

• 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: N-Boc-2-methyl-6-piperidine-carboxaldehyde
• 英文别名: tert-butyl (2S,6S)-2-formyl-6-methylpiperidine-1-carboxylate
• 化学式: C₁₂H₂₁NO₃
• 分子量: 227.304
• InChiKey: MEPVKWLQCNICCR-UWVGGRQHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 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：

  N-Boc-2-methyl-6-piperidine-carboxaldehyde 在 palladium on activated charcoal 正丁基锂 、 氢气 作用下， 以 乙醇 为溶剂， 反应 0.17h， 生成 1-哌啶羧酸,2-甲基-6-丙基-,1,1-二甲基乙基酯,(2R,6S)-rel-
  参考文献：
  名称：

  .alpha.-Lithioamine synthetic equivalents: syntheses of diastereoisomers from Boc derivatives of cyclic amines

  摘要：

  Sequences of alpha'-lithiations and electrophilic substitutions of Boc-pyrrolidines, Boc-piperidines, and Boc-hexahydroazepines that provide compounds which are substituted adjacent to nitrogen are reported, and the pathways of the reactions are discussed. By this methodology monosubstituted 2 and disubstituted 2,4,2,6, and 2,5 Boc-piperidines are obtained as single or separable diastereoisomers consistent with equatorial lithiations and retentive electrophilic substitution in chair conformations. Both cis and trans 2,6-disubstituted diastereoisomers can be prepared, and control of diastereoselectivity is demonstrated by syntheses of solenopsin A, a 2,6-trans-disubstituted piperidine, and of Boc-dihydropinidine, a 2,6-cis-disubstituted piperidine. In the case of 3-methoxy-Boc-piperidine elimination of methoxide occurs upon lithiation, and with cis-2,4-disubstituted Boc-piperidines the electrophile is introduced with trans stereochemistry at C-6. These reactions are suggested to involve twist boat conformations consistent with an X-ray crystal structure of 2-methyl-6-(trimethylstannyl)-4-phenyl-N-Boc-piperidine. Boc-pyrrolidine lithiates more rapidly than Boc-piperidine, provides 2-substituted products with electrophiles, and on further lithiation-substitution gives 2,5-cis- and -trans-substituted products. Boc-perhydroazepine provides 2-substituted products by the sequence and on further lithiation-substitution gives 2,7-trans-disubstituted products.

  DOI：

  10.1021/jo00057a024
• 作为产物：
  描述：

  1-Boc-哌啶 在 四甲基乙二胺 、 仲丁基锂 作用下， 反应 3.67h， 生成 N-Boc-2-methyl-6-piperidine-carboxaldehyde
  参考文献：
  名称：

  .alpha.-Lithioamine synthetic equivalents: syntheses of diastereoisomers from Boc derivatives of cyclic amines

  摘要：

  Sequences of alpha'-lithiations and electrophilic substitutions of Boc-pyrrolidines, Boc-piperidines, and Boc-hexahydroazepines that provide compounds which are substituted adjacent to nitrogen are reported, and the pathways of the reactions are discussed. By this methodology monosubstituted 2 and disubstituted 2,4,2,6, and 2,5 Boc-piperidines are obtained as single or separable diastereoisomers consistent with equatorial lithiations and retentive electrophilic substitution in chair conformations. Both cis and trans 2,6-disubstituted diastereoisomers can be prepared, and control of diastereoselectivity is demonstrated by syntheses of solenopsin A, a 2,6-trans-disubstituted piperidine, and of Boc-dihydropinidine, a 2,6-cis-disubstituted piperidine. In the case of 3-methoxy-Boc-piperidine elimination of methoxide occurs upon lithiation, and with cis-2,4-disubstituted Boc-piperidines the electrophile is introduced with trans stereochemistry at C-6. These reactions are suggested to involve twist boat conformations consistent with an X-ray crystal structure of 2-methyl-6-(trimethylstannyl)-4-phenyl-N-Boc-piperidine. Boc-pyrrolidine lithiates more rapidly than Boc-piperidine, provides 2-substituted products with electrophiles, and on further lithiation-substitution gives 2,5-cis- and -trans-substituted products. Boc-perhydroazepine provides 2-substituted products by the sequence and on further lithiation-substitution gives 2,7-trans-disubstituted products.

  DOI：

  10.1021/jo00057a024

文献信息

• The use of the aza-Diels–Alder reaction in the synthesis of pinidine and other piperidine alkaloids
  作者：Patrick D Bailey、Peter D Smith、Keith M Morgan、Georgina M Rosair

  DOI：10.1016/s0040-4039(01)02149-9

  日期：2002.2

  accessed; the benzhydryl group confers high diastereocontrol for derivatising the six-membered ring, allowing access to 2,5,6-trisubstituted piperidines, and to 2,6-disubstituted piperidines such as pinidine.

  亚胺博士2 CHNCHCO 2的Et，从二苯甲基胺和乙醛酸乙酯生成，提供了一种狄尔斯-阿尔德加合物与1,3-戊二烯从中范围的顺式-2,6-二取代的哌啶可以访问; 苯甲基使六元环衍生化具有较高的非对映异构控制性，从而可与2,5,6-三取代的哌啶和2,6-二取代的哌啶（例如吡啶）接触。
• Derivatives of N-[phenyl(alkylpiperidine-2-yl)methyl]benzamide, preparation method thereof and application of same in therapeutics
  申请人：Dargazanli Gihad

  公开号：US20060223861A1

  公开（公告）日：2006-10-05

  Compounds of formula (I) as defined herein: are useful for treating behavioral disorders associated with dementia, psychoses, in particular schizophrenia (deficient form and productive form) and acute or chronic extrapyramidal symptoms induced by neuroleptics; for the treatment of various forms of anxiety, panic attacks, phobias, and compulsive obsessive disorders; for treating various forms of depression, including psychotic depression; for treating disorders caused by alcohol abuse or weaning from alcohol, sexual behavior disorders, eating disorders and for treating migraine. Moreover, the compounds of the invention may be used for treating painful muscle contracture in rheumatology and in acute spinal pathology; for treating spastic contractures of medullary or cerebral origin; for the symptomatic treatment of acute and subacute pain of light to moderate intensity; for treating intense and/or chronic pain, neurogenic pain and intractable pain; for treating Parkinson's disease and Parkinson-like symptoms of neurodegenerative origin or induced by neuroleptics; for treating partial primary and secondary generalized epilepsy of simple or complex symptomology, mixed forms and other epileptic syndromes in addition to another antiepileptic treatment, or in monotherapy, for the treatment of sleep apnea, and for neuroprotection.

  本发明的化合物（I）的化学式如下：用于治疗与痴呆相关的行为障碍，精神病，特别是精神分裂症（缺乏型和产生型）以及由神经类药物引起的急性或慢性锥体外症状；用于治疗各种形式的焦虑、恐慌发作、恐惧症和强迫性妄想症；用于治疗各种形式的抑郁症，包括精神抑郁症；用于治疗由酒精滥用或戒酒引起的障碍，性行为障碍，进食障碍以及治疗偏头痛。此外，本发明的化合物可用于治疗风湿病学中的疼痛性肌肉挛缩和急性脊柱病理学；用于治疗由脊髓或大脑起源的痉挛性挛缩；用于对轻到中度强度的急性和亚急性疼痛进行症状性治疗；用于治疗剧烈和/或慢性疼痛，神经源性疼痛和难治性疼痛；用于治疗帕金森病和由神经类药物引起的神经退行性症状或帕金森样症状；用于治疗简单或复杂症状学、混合形式和其他癫痫综合征的部分原发性和继发性全身性癫痫，除了其他抗癫痫治疗外，还可单独使用，用于治疗睡眠呼吸暂停症，以及用于神经保护。
• Total Synthesis of Himandravine
  作者：Samuel Chackalamannil、Robert Davies、Andrew T. McPhail

  DOI：10.1021/ol010038w

  日期：2001.5.1

  [GRAPHICS]The first total synthesis of (+)-himandravine (1) is described, starting from (2S,6S)-cis-2-formyl-6-methyl-N-Boc-piperidine (8) in 11 linear steps and 17% overall yield. The key step involves a highly diastereoselective intramolecular Diels-Alder reaction of the key intermediate 5 that contains the entire latent carbon framework and functional group substitution of himandravine.
• 2,6-Disubstituted N-arylsulfonyl piperidines as γ-secretase inhibitors
  作者：Dmitri A. Pissarnitski、Theodros Asberom、Thomas A. Bara、Alex V. Buevich、John W. Clader、William J. Greenlee、Henry S. Guzik、Hubert B. Josien、Wei Li、Michael McEwan、Brian A. McKittrick、Terry L. Nechuta、Eric M. Parker、Lisa Sinning、Elizabeth M. Smith、Lixin Song、Henry A. Vaccaro、Johannes H. Voigt、Lili Zhang、Qi Zhang、Zhiqiang Zhao

  DOI：10.1016/j.bmcl.2006.09.094

  日期：2007.1

  A novel piperidine series of gamma-secretase inhibitors, potentially useful for the treatment of Alzheimer's disease, is disclosed. SAR investigation revealed the requirement for cis-stereochemistry of the substituents attached to the core, which resulted in the chair-like diaxial conformation of the piperidine ring. The series was optimized to provide inhibitors with IC(50)'s in the single-digit nanomolar range. Absolute stereochemistry of the active enantiomer was assigned. (c) 2006 Elsevier Ltd. All rights reserved.
• The Bromopentadienyl Acrylate Approach to Himbacine
  作者：Leon S.-M. Wong、Lisa A. Sharp、Natacha M. C. Xavier、Peter Turner、Michael S. Sherburn

  DOI：10.1021/ol0259746

  日期：2002.5.1

  [GRAPHICS]The syntheses of 4,4a-didehydrohimbacine and 4,4a-didehydrohimandravine are presented. Key steps include an intramolecular Diels-Alder reaction of a bromopentadienyl acrylate and Suzuki-Miyaura and Stille coupling reactions.