(+/-)-1-Methyl-3-acetoxypiperidin | 6659-33-2

• 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: (+/-)-1-Methyl-3-acetoxypiperidin
• 英文别名: 3-Acetoxy-1-methyl-piperidin；Essigsaeure-<1-Methyl-piperidyl-(3)-ester>；1-Methylpiperidin-3-ol Acetat；1-Methyl-3-acetoxy-azacyclohexane；(1-methylpiperidin-3-yl) acetate
• CAS: 6659-33-2
• 化学式: C₈H₁₅NO₂
• mdl: MFCD13184005
• 分子量: 157.213
• InChiKey: CTVJTRDKSBQDGV-UHFFFAOYSA-N

物化性质

• 沸点：
  72 °C(Press: 11 Torr)
• 密度：
  1.02±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.875
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (+/-)-1-Methyl-3-acetoxypiperidin 在 Candida antarctica lipase B 、 环戊醇 、 环戊基甲醚 、 三乙胺 作用下， 以 甲醇 为溶剂， 反应 96.0h， 生成 1-甲基-(R)-3-羟基哌啶
  参考文献：
  名称：

  (R)-3-Hydroxy-N-methylpiperidine, (R)-Mepenzolate 的合成关键中间体, 基于外消旋形式的脂肪酶催化拆分的制备

  摘要：

  In this study, a two-step method for the gram-scale synthesis of (R)-3-hydroxy-N-methylpiperidine in 97.8% enantiomeric excess (ee) is reported. The key chiral synthetic intermediate of (R)-mepenzolate was formed in 22% yield over two steps using a commercially available and inexpensive racemic alcohol as the starting material. In the first step, Candida antarctica lipase B-catalyzed kinetic resolution of the racemic alcohol under acetylation conditions was performed to obtain the acetate form of the (R)-enantiomer in 82.1% ee (E 18). The second step involved enantio-enrichment using the same lipase to catalyze deacetylation. The ee of the product (R)-alcohol was further enriched to 97.8%.

  DOI：

  10.3987/com-16-s(s)28
• 作为产物：
  描述：

  3-羟基-1-甲基哌啶 、 乙酸酐 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.33h， 以88%的产率得到(+/-)-1-Methyl-3-acetoxypiperidin
  参考文献：
  名称：

  1H-nmr光谱法测定3-乙酰氨基-和3-乙酰氧基-哌啶和-四氢吡喃的gauche效应

  摘要：

  摘要采用低温1 Hn.mr光谱法测定了乙酰氨基和乙酰氧基的A值。在室温下获得了新制备的反式-（22）和顺式-5-乙酰氧基-2-（1-羟基-1-甲基乙基）四氢吡喃（24）的相关邻位偶合常数的极限值。在低温（积分）和室温（带宽和耦合常数）下，通过1 Hn.mr光谱研究了AcNH-3和AcO-3在哌啶，哌啶三氟乙酸盐和四氢吡喃中的吸引效应。在低温下获得的结果更可靠。N-（3-哌啶基）乙酰胺（11），N-（1-甲基-3-哌啶基）乙酰胺（12）的构象平衡位置

  DOI：

  10.1016/0008-6215(90)84017-o

文献信息

• [EN] NEW COMPOUNDS, PHARMACEUTICAL COMPOSITION AND METHODS RELATING THERETO<br/>[FR] NOUVEAUX COMPOSÉS, COMPOSITION PHARMACEUTIQUE ET PROCÉDÉS CORRESPONDANTS
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2010149684A1

  公开（公告）日：2010-12-29

  New compounds are disclosed which have utility in the treatment of a variety of metabolic related conditions in a patient. The compounds of this invention have the structure (I): wherein R1, R2, R3, n, p, q, and Ar are as defined herein, including stereoisomers, solvates and pharmaceutically acceptable salts thereof. Also disclosed are pharmaceutical compositions comprising a compound of this invention, as well as methods relating to the use thereof in a patient in need thereof.

  本发明公开了具有结构(I)的新化合物，其在患者中治疗各种与代谢相关的病症具有实用性：其中R1、R2、R3、n、p、q和Ar如本文所定义，包括立体异构体、溶剂合物和药学上可接受的盐。还公开了包含本发明化合物的药物组合物，以及关于其在有需要的患者中使用的方法。
• Determination of the gauche effect of 3-acetamido- and 3-acetoxy-piperidine and -tetrahydropyran by 1H-n.m.r. spectroscopy
  作者：Bruno Bernet、Umberto Piantini、Andrea Vasella

  DOI：10.1016/0008-6215(90)84017-o

  日期：1990.9

  H-n.m.r. spectroscopy. The limiting values for the relevant vicinal coupling constants of the newly prepared trans - ( 22 ) and cis -5-acetoxy-2-(1-hydroxy-1-methylethyl)tetrahydropyran ( 24 ) were obtained at room temperature. The attractive gauche effect of AcNH-3 and AcO-3 in piperidines, piperidinium trifluoroacetates, and tetrahydropyrans was investigated by 1 H-n.m.r. spectroscopy both at low temperature

  摘要采用低温1 Hn.mr光谱法测定了乙酰氨基和乙酰氧基的A值。在室温下获得了新制备的反式-（22）和顺式-5-乙酰氧基-2-（1-羟基-1-甲基乙基）四氢吡喃（24）的相关邻位偶合常数的极限值。在低温（积分）和室温（带宽和耦合常数）下，通过1 Hn.mr光谱研究了AcNH-3和AcO-3在哌啶，哌啶三氟乙酸盐和四氢吡喃中的吸引效应。在低温下获得的结果更可靠。N-（3-哌啶基）乙酰胺（11），N-（1-甲基-3-哌啶基）乙酰胺（12）的构象平衡位置
• Iorio; Gatta; Michalek, European Journal of Medicinal Chemistry, 1980, vol. 15, # 2, p. 165 - 171
  作者：Iorio、Gatta、Michalek

  DOI：——

  日期：——
• Dubravkova et al., Chemicke Zvesti, 1956, vol. 10, p. 421,423
  作者：Dubravkova et al.

  DOI：——

  日期：——
• Preparation of (R)-3-Hydroxy-N-methylpiperidine, a Synthetic Key Intermediate of (R)-Mepenzolate, Based on the Lipase-Catalyzed Resolution of the Racemic Form
  作者：Takeshi Sugai、Yasunobu Yamashita、Kengo Hanaya、Mitsuru Shoji

  DOI：10.3987/com-16-s(s)28

  日期：——

  In this study, a two-step method for the gram-scale synthesis of (R)-3-hydroxy-N-methylpiperidine in 97.8% enantiomeric excess (ee) is reported. The key chiral synthetic intermediate of (R)-mepenzolate was formed in 22% yield over two steps using a commercially available and inexpensive racemic alcohol as the starting material. In the first step, Candida antarctica lipase B-catalyzed kinetic resolution of the racemic alcohol under acetylation conditions was performed to obtain the acetate form of the (R)-enantiomer in 82.1% ee (E 18). The second step involved enantio-enrichment using the same lipase to catalyze deacetylation. The ee of the product (R)-alcohol was further enriched to 97.8%.