(S)-(4-Methoxy-phenyl)-((2S,6R)-6-methyl-piperidin-2-yl)-methanol

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (S)-(4-Methoxy-phenyl)-((2S,6R)-6-methyl-piperidin-2-yl)-methanol
• 英文别名: (S)-(4-methoxyphenyl)-[(2S,6R)-6-methylpiperidin-2-yl]methanol
• 化学式: C₁₄H₂₁NO₂
• 分子量: 235.326
• InChiKey: LOENSLGSYGROQH-SWHYSGLUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  41.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1-Boc-哌啶 在 sodium hydroxide 、 四甲基乙二胺 、 仲丁基锂 作用下， 以 乙醇 为溶剂， 反应 3.0h， 生成 (S)-(4-Methoxy-phenyl)-((2S,6R)-6-methyl-piperidin-2-yl)-methanol
  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

• [EN] BETA-HYDROXY HETEROCYCLIC AMINES AND THEIR USE IN THE TREATMENT OF HYPERGLYCAEMIA<br/>[FR] AMINES HÉTÉROCYCLIQUES BÊTA-HYDROXY ET LEUR UTILISATION DANS LE TRAITEMENT DE L'HYPERGLYCÉMIE
  申请人：ATROGI AB

  公开号：WO2019053425A1

  公开（公告）日：2019-03-21

  There is herein provided a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein X, R1, ring A, m and n have meanings as provided in the description.

  在此提供了一个式子(I)的化合物或其药用可接受的盐，其中X、R1、环A、m和n的含义如描述中所提供。
• .alpha.-Lithioamine synthetic equivalents: syntheses of diastereoisomers from the Boc-piperidines
  作者：Peter Beak、Won Koo Lee

  DOI：10.1021/jo00296a008

  日期：1990.4
• BETA-HYDROXY HETEROCYCLIC AMINES AND THEIR USE IN THE TREATMENT OF HYPERGLYCAEMIA
  申请人：Atrogi AB

  公开号：EP3681862A1

  公开（公告）日：2020-07-22
• .alpha.-Lithioamine synthetic equivalents: syntheses of diastereoisomers from Boc derivatives of cyclic amines
  作者：Peter Beak、Won Koo Lee

  DOI：10.1021/jo00057a024

  日期：1993.2

  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.