(3S,4S)-4-<(1S)-1-benzyloxycarbonylethyl>-3-<(1R)-1-tert-butyldimethylsilyloxyethyl>-2-azetidinone | 96035-98-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: (3S,4S)-4-<(1S)-1-benzyloxycarbonylethyl>-3-<(1R)-1-tert-butyldimethylsilyloxyethyl>-2-azetidinone
• 英文别名: (3S,4S)-3-<(R)-1-(t-Butyldimethylsilyloxy)ethyl>-4-<(S)-1-(benzyloxycarbonyl)ethyl>-2-azetidinone；benzyl (2S)-2-[(2S,3S)-3-[(1R)-1-[tert-butyl(dimethyl)silyl]oxyethyl]-4-oxoazetidin-2-yl]propanoate
• CAS: 96035-98-2；96093-92-4
• 化学式: C₂₁H₃₃NO₄Si
• 分子量: 391.583
• InChiKey: IALHZITVANRGAL-BURFUSLBSA-N

物化性质

• 熔点：
  69-70 °C
• 沸点：
  478.1±15.0 °C(Predicted)
• 密度：
  1.049±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.89
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3S,4S)-4-<(1S)-1-benzyloxycarbonylethyl>-3-<(1R)-1-tert-butyldimethylsilyloxyethyl>-2-azetidinone 在 palladium on activated charcoal 氢气 作用下， 以 乙醚 、 乙酸乙酯 为溶剂， 反应 4.0h， 生成 (3S,4S)-3-<(1R)-1-<(tert-Butyldimethylsilyl)oxy>ethyl>-4-<(1S)-1-(methoxycarbonyl)ethyl>azetidin-2-one
  参考文献：
  名称：

  Highly stereocontrolled synthesis of the 1β-methylcarbapenem key intermediate by the reformatsky reaction of 3-(2-bromopropionyl)-2-oxazolidone derivatives with a 4-acetoxy-2-azetidinone

  摘要：

  The key synthetic intermediate (4) of 1-beta-methylcarbapenems (1 approximately 3) was efficiently synthesized by employing highly stereocontrolled Reformatsky reaction (C4-alkylation) of 3-(2-bromopropionyl)-2-oxazolidone derivatives (6) with (3R,4R)-4-acetoxy-3-[(R)-1-(t-butyldimethylsilyloxy)ethyl]-2-azetidinone (5) in the presence of zinc dust followed by removal of 2-oxazolidone moieties. The best diastereoselectivity (beta:alpha = 95.5) could be realized by uses of sterically crowded achiral 2-oxazolidone derivatives such as 4,4-dimethyl-, 4,4,5,5-tetramethyl, and 4,4-dibutyl-5,5-pentamethylene-2-oxazolidone and higher reaction temperatures (refluxing tetrahydrofran). The remarkable diastereoselectivities observed for the Reformatsky reactions could be explained by means of the weakly chelating transition state models.

  DOI：

  10.1016/s0040-4020(01)87086-1
• 作为产物：
  描述：

  (3S,4R)-3-<(R)-1-(t-Butyldimethylsilyloxy)ethyl>-4-<(S)-1-(4,4-dimethyl-2-oxazolidone-3-carbonyl)ethyl>-2-azetidinone 生成 (3S,4S)-4-<(1S)-1-benzyloxycarbonylethyl>-3-<(1R)-1-tert-butyldimethylsilyloxyethyl>-2-azetidinone
  参考文献：
  名称：

  TEHRADZIMA, ATSURO;ITO, JOSIO;KAVABATA, TAKEHO;SAKAI, KUNIKADZU;XIYAMA, T+

  摘要：

  DOI：

文献信息

• Syntheses of chiral intermediates of 1-β-methylcarbapenems: (3<i>S</i>,4<i>R</i>)-3-[1(<i>R</i>)-<i>tert</i>-butyldimethylsilyloxyethyl]-4-chloroazetidin-2-one and (3<i>S</i>,4<i>S</i>)-3-[1(<i>R</i>)-<i>tert</i>-butyldimethylsilyloxyethyl]-4-[1(<i>R</i>)-<i>tert</i>-butylthiocarbonylethyl]azetidin-2-one
  作者：Masaki Endo

  DOI：10.1139/v87-357

  日期：1987.9.1

  The 4-chloroazetidinone 10, a very reactive chiral intermediate for 1-β-methylcarbapenems (1b), was easily prepared and isolated as a solid crystalline compound from the corresponding sulfide 5. Another chiral intermediate (16d) bearing the 1-β-methyl moiety was prepared by stereoselective aldol type condensation of either azetidinone 4 or 10 with metal enolates 14 (R = S—Bu′, M = ZrCp₂Cl, [Formula: see text], and SnBr). The β/α ratios were 9:1, 3:1, 2:1 respectively.

  4-氯吡嗪酮10是1-β-甲基卡巴比林（1b）的非常活性手性中间体，可以从相应的硫醚5中轻松制备并分离为固体结晶化合物。另一个携带1-β-甲基基团的手性中间体（16d）是通过对吡嗪酮4或10与金属烯醇酸盐14（R = S—Bu'，M = ZrCp2Cl，[Formula: see text]和SnBr）的立体选择性醛缩反应制备的。β/α比例分别为9:1，3:1，2:1。
• Synthetic Studies of Carbapenem and Penem Antibiotics. V. Efficient Synthesis of the 1.BETA.-Methylcarbapenem Skeleton.
  作者：Makoto SUNAGAWA、Akira SASAKI、Haruki MATSUMURA、Koshiro GODA、Katsumi TAMOTO

  DOI：10.1248/cpb.42.1381

  日期：——

  An efficient synthesis of 1β-methylcarbapenem from the 1-(2-oxoazetidinyl)acetate 8 was developed by application of the Dieckmann reaction. Dieckmann-type cyclization of 8 and conversion to the enolphosphate 10 were achieved without epimerization to the 1α-methyl isomer in a one-pot procedure. Treatment with the mercaptan 22 after the phosphorylation resulted in a practical one-pot preparation of the 1β-methylcarbapenem derivative 23 from 8.

  通过应用 Dieckmann 反应，开发了从 1-(2-氧代氮杂环丁酯)乙酸酯 8 高效合成 1β-甲基碳青霉烯的方法。 8 的 Dieckmann 型环化和烯醇磷酸 10 的转化是通过一锅法实现的，无需差向异构化为 1α-甲基异构体。磷酸化后用硫醇22处理导致从8中一锅法制备出1β-甲基碳青霉烯衍生物23。
• TEHRADZIMA, ATSURO;ITO, JOSIO;KAVABATA, TAKEHO;SAKAI, KUNIKADZU;XIYAMA, T+
  作者：TEHRADZIMA, ATSURO、ITO, JOSIO、KAVABATA, TAKEHO、SAKAI, KUNIKADZU、XIYAMA, T+

  DOI：——

  日期：——
• Highly stereocontrolled synthesis of the 1β-methylcarbapenem key intermediate by the reformatsky reaction of 3-(2-bromopropionyl)-2-oxazolidone derivatives with a 4-acetoxy-2-azetidinone
  作者：Yoshio Ito、Akira Sasaki、Kastumi Tamoto、Makoto Sunagawa、Shiro Terashima

  DOI：10.1016/s0040-4020(01)87086-1

  日期：1991.1

  The key synthetic intermediate (4) of 1-beta-methylcarbapenems (1 approximately 3) was efficiently synthesized by employing highly stereocontrolled Reformatsky reaction (C4-alkylation) of 3-(2-bromopropionyl)-2-oxazolidone derivatives (6) with (3R,4R)-4-acetoxy-3-[(R)-1-(t-butyldimethylsilyloxy)ethyl]-2-azetidinone (5) in the presence of zinc dust followed by removal of 2-oxazolidone moieties. The best diastereoselectivity (beta:alpha = 95.5) could be realized by uses of sterically crowded achiral 2-oxazolidone derivatives such as 4,4-dimethyl-, 4,4,5,5-tetramethyl, and 4,4-dibutyl-5,5-pentamethylene-2-oxazolidone and higher reaction temperatures (refluxing tetrahydrofran). The remarkable diastereoselectivities observed for the Reformatsky reactions could be explained by means of the weakly chelating transition state models.