Ethyl 4(S)-benzyl-3-(benzyloxycarbonyl)-2,2-dimethyl-5(R)-oxazolidineacetate | 158744-39-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: Ethyl 4(S)-benzyl-3-(benzyloxycarbonyl)-2,2-dimethyl-5(R)-oxazolidineacetate
• 英文别名: benzyl (4S,5R)-4-benzyl-5-(2-ethoxy-2-oxoethyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate
• CAS: 158744-39-9
• 化学式: C₂₄H₂₉NO₅
• 分子量: 411.498
• InChiKey: MKSMZLZARUAMEI-LEWJYISDSA-N

物化性质

• 沸点：
  519.4±45.0 °C(Predicted)
• 密度：
  1.143±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  65.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Ethyl 4(S)-benzyl-3-(benzyloxycarbonyl)-2,2-dimethyl-5(R)-oxazolidineacetate 在 palladium on activated charcoal N-乙基吗啉 、 盐酸 、 4-二甲氨基吡啶 、 氢氧化钾 、 sodium hydroxide 、 草酰氯 、 三氯溴甲烷 、 氢气 、 2-mercaptopyridine-1-oxide sodium salt 、 溶剂黄146 、 1-羟基苯并三唑一水物 、 N,N-二甲基甲酰胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 异丙醇 、 甲苯 为溶剂， 反应 152.0h， 生成 沙喹那韦
  参考文献：
  名称：

  Studies toward the Large-Scale Synthesis of the HIV Proteinase Inhibitor Ro 31-8959

  摘要：

  Ro 31-8959 (1), a potent and selective inhibitor of HIV proteinase, is currently in phase III clinical trials. Six approaches for the large-scale synthesis of this compound have been studied. All routes employ an initial disconnection to an electrophilic L-phenylalanine homologue equivalent 13 and the decahydroisoquinoline derivative 5. They differ in adopting either an epoxide, a cyclic sulfate, or an aldehyde as the electrophilic entity and develop chirality from L-phenylalanine, dimethyl D-tartrate, or a Sharpless epoxidation. The preferred route starts from N-phthaloyl-L-phenylalaninyl chloride and uses tris((trimethylsilyl)oxy)ethene to effect homologation to hydroxy ketone 30, which is elaborated in a five-step two-pot procedure to N-phthaloyl epoxide 33 and hence 1. Kilogram quantities of Ro 31-8959 have been prepared using this route.

  DOI：

  10.1021/jo00092a026
• 作为产物：
  描述：

  N-苄氧羰基-L-苯丙氨酸 在 sodium tetrahydroborate 、 对甲苯磺酸 、 N,N'-羰基二咪唑 作用下， 以 乙醇 为溶剂， 反应 6.0h， 生成 Ethyl 4(S)-benzyl-3-(benzyloxycarbonyl)-2,2-dimethyl-5(R)-oxazolidineacetate
  参考文献：
  名称：

  Studies toward the Large-Scale Synthesis of the HIV Proteinase Inhibitor Ro 31-8959

  摘要：

  Ro 31-8959 (1), a potent and selective inhibitor of HIV proteinase, is currently in phase III clinical trials. Six approaches for the large-scale synthesis of this compound have been studied. All routes employ an initial disconnection to an electrophilic L-phenylalanine homologue equivalent 13 and the decahydroisoquinoline derivative 5. They differ in adopting either an epoxide, a cyclic sulfate, or an aldehyde as the electrophilic entity and develop chirality from L-phenylalanine, dimethyl D-tartrate, or a Sharpless epoxidation. The preferred route starts from N-phthaloyl-L-phenylalaninyl chloride and uses tris((trimethylsilyl)oxy)ethene to effect homologation to hydroxy ketone 30, which is elaborated in a five-step two-pot procedure to N-phthaloyl epoxide 33 and hence 1. Kilogram quantities of Ro 31-8959 have been prepared using this route.

  DOI：

  10.1021/jo00092a026

文献信息

• Studies toward the Large-Scale Synthesis of the HIV Proteinase Inhibitor Ro 31-8959
  作者：Kevin E. B. Parkes、David J. Bushnell、Peter H. Crackett、Stephen J. Dunsdon、Andrew C. Freeman、Michelle P. Gunn、Richard A. Hopkins、Robert W. Lambert、Joseph A. Martin

  DOI：10.1021/jo00092a026

  日期：1994.7

  Ro 31-8959 (1), a potent and selective inhibitor of HIV proteinase, is currently in phase III clinical trials. Six approaches for the large-scale synthesis of this compound have been studied. All routes employ an initial disconnection to an electrophilic L-phenylalanine homologue equivalent 13 and the decahydroisoquinoline derivative 5. They differ in adopting either an epoxide, a cyclic sulfate, or an aldehyde as the electrophilic entity and develop chirality from L-phenylalanine, dimethyl D-tartrate, or a Sharpless epoxidation. The preferred route starts from N-phthaloyl-L-phenylalaninyl chloride and uses tris((trimethylsilyl)oxy)ethene to effect homologation to hydroxy ketone 30, which is elaborated in a five-step two-pot procedure to N-phthaloyl epoxide 33 and hence 1. Kilogram quantities of Ro 31-8959 have been prepared using this route.