(R)-N-(cyclopropylmethyl)oripavine ammonium bromide | 1252784-89-6

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 英文名称: (R)-N-(cyclopropylmethyl)oripavine ammonium bromide
• 英文别名: (3R,4R,7aR,12bS)-3-(cyclopropylmethyl)-7-methoxy-3-methyl-2,4,7a,13-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-3-ium-9-ol;bromide
• CAS: 1252784-89-6
• 化学式: Br*C₂₂H₂₆NO₃
• 分子量: 432.357
• InChiKey: SVOACLJWPIBSJS-DNZSWPBUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.05
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  38.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-N-(cyclopropylmethyl)oripavine ammonium bromide 在 甲酸 、 palladium 10% on activated carbon 、 氢气 、 氧气 、 tetraphenylporphyrin 、 硫脲 作用下， 以 甲醇 、 二氯甲烷 、 水 、 异丙醇 为溶剂， 5.0~15.0 ℃ 、275.8 kPa 条件下， 反应 34.0h， 生成 (R)-methylnaltrexone bromide
  参考文献：
  名称：

  Synthesis of Naltrexone and (R)-Methylnaltrexone from Oripavine via Direct Oxidation of Its Quaternary Salts

  摘要：

  (R)-Methylnaltrexone and naltrexone were each prepared in four steps from oripavine in practical yields. The procedure involved quaternization of oripavine with cyclopropylmethyl halides, singlet oxygen oxidation of the quaternary salts, and the reduction of endo peroxides to 14-hydroxyketone functionalities. (R)-Methylnaltrexone was prepared from the corresponding R-diastereomer of the oripavine salt. All diastereomeric mixtures of the quaternary salts were subjected to N-demethylation with sodium thiolate to yield cyclopropyl methylnororipavine, which was converted into naltrexone by peracid oxidation and hydrogenation according to established procedures.

  DOI：

  10.1055/s-0034-1378808
• 作为产物：
  描述：

  在 Dowex-1 resin (strongly basic bromine loaded, 50-100 mesh) 作用下， 以 甲醇 、 水 为溶剂， 生成 (S)-N-(cyclopropylmethyl)oripavine ammonium bromide 、 (R)-N-(cyclopropylmethyl)oripavine ammonium bromide
  参考文献：
  名称：

  [EN] PROCESSES FOR THE PREPARATION OF MORPHINANE AND MORPHINONE COMPOUNDS
  [FR] PROCÉDÉS POUR LA PRÉPARATION DE COMPOSÉS DE MORPHINANE ET DE MORPHINONE

  摘要：

  本申请描述了合成吗啡烷和吗啡酮化合物的过程，这些化合物可用作药物。还包括在制备这些化合物过程中有用的新型中间体。该过程包括对奥利帕定进行季铵化，以提供R-和S-异构体（在氮上）季铵盐的混合物。R-异构体容易被分离并转化为各种N-(R)-吗啡烷和N-(S)-吗啡酮化合物。R-异构体、S-异构体或R-和S-异构体的混合物可以被去甲基化并转化为各种吗啡烷和吗啡酮化合物。

  公开号：

  WO2010121369A1

文献信息

• Synthesis of Buprenorphine from Oripavine via N-Demethylation of Oripavine Quaternary Salts
  作者：Lukas Werner、Ales Machara、David R. Adams、D. Phillip Cox、Tomas Hudlicky

  DOI：10.1021/jo200567n

  日期：2011.6.3

  synthesized from oripavine by a sequence involving the conversion of oripavine into its cyclopropylmethyl quaternary salt, N-demethylation with thiolate to N-cyclopropylmethyl nororipavine, and conversion of this material to the title compound by previously available methods. The new synthesis avoids toxic reagents used previously, is shorter, and proceeds in comparable yields. Experimental and spectral data

  丁丙诺啡是通过以下顺序从兽皮中合成的，该序列涉及将兽皮中的碳转化为其环丙基甲基季盐，用硫醇盐进行N-脱甲基化为N-环丙基甲基去甲紫罗兰，然后通过先前可获得的方法将该物质转化为标题化合物。新的合成方法避免了以前使用的有毒试剂，时间更短，并且收率相当。提供了所有新化合物的实验数据和光谱数据。
• [EN] PROCESSES FOR THE PREPARATION OF MORPHINANE AND MORPHINONE COMPOUNDS<br/>[FR] PROCÉDÉS POUR LA PRÉPARATION DE COMPOSÉS DE MORPHINANE ET DE MORPHINONE
  申请人：UNIV BROCK

  公开号：WO2010121369A1

  公开（公告）日：2010-10-28

  The present application describes processes for the synthesis of morphinane and morphinone compounds, useful as pharmaceutical agents. Also included are novel intermediates useful in the preparation of these compounds. The process comprises quaternization of oripavine to provide a mixture of the R- and S-isomeric (at the nitrogen) quaternary salts. The R-isomer is readily isolated and converted to various N-(R)-morphinane and N-(S)-morphinone compounds. The R-isomer, S-isomer or a mixture of R- and S-isomers may be demethylated and converted to various morphinane and morphinone compounds.

  本申请描述了合成吗啡烷和吗啡酮化合物的过程，这些化合物可用作药物。还包括在制备这些化合物过程中有用的新型中间体。该过程包括对奥利帕定进行季铵化，以提供R-和S-异构体（在氮上）季铵盐的混合物。R-异构体容易被分离并转化为各种N-(R)-吗啡烷和N-(S)-吗啡酮化合物。R-异构体、S-异构体或R-和S-异构体的混合物可以被去甲基化并转化为各种吗啡烷和吗啡酮化合物。
• Synthesis of Naltrexone and (R)-Methylnaltrexone from Oripavine via Direct Oxidation of Its Quaternary Salts
  作者：Tomas Hudlicky、Ales Machara、Lukas Werner、Hannes Leisch、Robert Carroll、David Adams、D. Haque、D. Cox

  DOI：10.1055/s-0034-1378808

  日期：——

  (R)-Methylnaltrexone and naltrexone were each prepared in four steps from oripavine in practical yields. The procedure involved quaternization of oripavine with cyclopropylmethyl halides, singlet oxygen oxidation of the quaternary salts, and the reduction of endo peroxides to 14-hydroxyketone functionalities. (R)-Methylnaltrexone was prepared from the corresponding R-diastereomer of the oripavine salt. All diastereomeric mixtures of the quaternary salts were subjected to N-demethylation with sodium thiolate to yield cyclopropyl methylnororipavine, which was converted into naltrexone by peracid oxidation and hydrogenation according to established procedures.