(+)-8,8-二氯樟脑磺哑嗪 | 127184-05-8

• 物质功能分类: 化学试剂 - 手性化学试剂
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 中文名称: (+)-8,8-二氯樟脑磺哑嗪
• 中文别名: (+)-3,3-二氯-2,N-环氧-外型-10,2-莰烷磺内酰胺
• 英文名称: (+)-(8,8-dichlorocamphorylsulfonyl)oxaziridine
• 英文别名: (1S,6R,8S)-7,7-dichloro-11,11-dimethyl-5-oxa-3λ6-thia-4-azatetracyclo[6.2.1.01,6.04,6]undecane 3,3-dioxide
• CAS: 127184-05-8
• 化学式: C₁₀H₁₃Cl₂NO₃S
• 分子量: 298.19
• InChiKey: HAMBQYFZDBYWHU-CNLAJYNUSA-N

物化性质

• 熔点：
  181-186 °C
• 沸点：
  390.5±52.0 °C(Predicted)
• 密度：
  1.68±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  58.1
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 危险等级：
  5.1
• 安全说明：
  S22,S24/25
• WGK Germany：
  3
• 包装等级：
  III
• 危险类别：
  5.1
• 危险品运输编号：
  UN 1479
• 危险性防范说明：
  P220,P261,P305+P351+P338
• 危险性描述：
  H271,H315,H319,H335

反应信息

• 作为产物：
  描述：

  (+)-((8,8-Dichlorocamphoryl)sulfonyl)imine 在 potassium carbonate 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 8.0h， 以98%的产率得到(+)-8,8-二氯樟脑磺哑嗪
  参考文献：
  名称：

  Chemistry of oxaziridines. 18. Synthesis and enantioselective oxidations of the [(8,8-dihalocamphoryl)sulfonyl]oxaziridines

  摘要：

  The synthesis and enantioselective oxidations of [(8,8-dihalocamphoryl)sulfonyl]oxaziridines [8,8-dichloro-1,7,7-trimethyl-2'-(phenylsulfonyl)spiro[bicyclo[2.2.1]heptane-2,3'-oxazinidine]] 13 are reported. These reagents are prepared in two steps from the (camphorylsulfonyl)imine 4 by treatment of the corresponding azaenolate with electrophilic halogen sources followed by biphasic oxidation of the resulting dihalo imine 6-9 with m-CPBA/K2CO3. Of these oxaziridines the dichloro reagent 13b, available on a multigram scale, affords the highest enantioselectivities for the asymmetric oxidation of sulfides to sulfoxides (42-74%) and for the hydroxylation of enolates (often better than 95% ee). In general the molecular recognition is predicted and explained in terms of minimization of nonbonded steric interactions the transition states. For the asymmetric oxidation of sulfides to sulfoxides, secondary electronic factors related to the polarity of the sulfide and oxaziridine also play a role. Definitive evidence for chelation of the metal enolate with the C-X bond in 13 is not found. The molecular recognition is interpreted in terms of the higher reactivity of the reagents and an active-site structure which is sterically complementary with the enolate. For the asymmetric hydroxylation of the Z- and E-enolates of propiophenone (16a), the Z-enolate exhibits much higher stereoselectivity than the E-enolate: >95% vs 22% ee.

  DOI：

  10.1021/jo00052a050
• 作为试剂：
  描述：

  苯基膦酸二乙酯 、 alkaline earth salt of/the/ methylsulfuric acid 在 吡啶 、 4-二甲氨基吡啶 、 四(三苯基膦)钯 、 草酰氯 、 sodium hexamethyldisilazane 、 5,5-二甲基-1,3-环己二酮 、 (+)-8,8-二氯樟脑磺哑嗪 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 苯 为溶剂， 反应 8.0h， 生成 dimethyl (S)-phenyl(hydroxy)methylphosphonate
  参考文献：
  名称：

  Chiral, non-racemic α-hydroxyphosphonates and phosphonic acids via stereoselective hydroxylation of diallyl benzylphosphonates

  摘要：

  Chiral, non-racemic alpha-hydroxyphosphonates have been prepared in high enantiomeric excess (96-98% ee), via stereoselective oxaziridine-mediated hydroxylation of diallyl benzylphosphonates. The enantiomeric purity and absolute configuration of the alpha-hydroxyphosphonates was established from H-1 and P-31 NMR spectroscopy of the (S)-O-methylmandelate esters. Deprotection of the diallyl alpha-hydroxyphosphonates under neutral conditions furnished the corresponding free phosphonic acids, retaining a high degree of stereochemical purity (90 to >98% ee). (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(02)00786-3

文献信息

• Neprilysin inhibitors
  申请人：THERAVANCE BIOPHARMA R&D IP, LLC

  公开号：US10336773B2

  公开（公告）日：2019-07-02

  In one aspect, the invention relates to compounds having the formula: where R1-R6, a, b, and X are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and processes and intermediates for preparing such compounds.

  一方面，本发明涉及具有以下式子的化合物： 其中 R1-R6、a、b 和 X 如说明书中所定义，或其药学上可接受的盐。这些化合物具有肾酶抑制活性。在另一方面，本发明涉及包含此类化合物的药物组合物；使用此类化合物的方法；以及制备此类化合物的工艺和中间体。
• NEPRILYSIN INHIBITORS
  申请人：THERAVANCE BIOPHARMA R&D IP, LLC

  公开号：US20170022219A1

  公开（公告）日：2017-01-26

  In one aspect, the invention relates to compounds having the formula: where R 1 -R 6 , a, b, and X are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and processes and intermediates for preparing such compounds.
• US9682052B2
  申请人：——

  公开号：US9682052B2

  公开（公告）日：2017-06-20
• US9688692B2
  申请人：——

  公开号：US9688692B2

  公开（公告）日：2017-06-27
• US9845332B2
  申请人：——

  公开号：US9845332B2

  公开（公告）日：2017-12-19