(3S,4S)-3-<(1R)-1-<(tert-Butyldimethylsilyl)oxy>ethyl>-4-<(1S)-1-(methoxycarbonyl)ethyl>azetidin-2-one | 87037-96-5

• 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)-3-<(1R)-1-<(tert-Butyldimethylsilyl)oxy>ethyl>-4-<(1S)-1-(methoxycarbonyl)ethyl>azetidin-2-one
• 英文别名: (3S,4S)-3-<(R)-1-(t-Butyldimethylsilyloxy)ethyl>-4-<(S)-1-(methoxycarbonyl)ethyl>-2-azetidinone；(3S,4R)-3-<(1R)-1-t-butyldimethylsilyloxyethyl>-4-<(1S)-1-methoxycarbonylethyl>-azetidin-2-one；(3S,4S)-3-[(R)-1-(t-Butyldimethylsilyloxy)ethyl]-4-[(S)-1-(methoxycarbonyl)ethyl]-2-azetidinone；methyl (2S)-2-[(2S,3S)-3-[(1R)-1-[tert-butyl(dimethyl)silyl]oxyethyl]-4-oxoazetidin-2-yl]propanoate
• CAS: 87037-96-5
• 化学式: C₁₅H₂₉NO₄Si
• 分子量: 315.485
• InChiKey: DQHPQIYSTKHMCQ-IRCOFANPSA-N

物化性质

• 沸点：
  382.7±7.0 °C(Predicted)
• 密度：
  1.009±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.32
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.87
• 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)-3-<(1R)-1-<(tert-Butyldimethylsilyl)oxy>ethyl>-4-<(1S)-1-(methoxycarbonyl)ethyl>azetidin-2-one 在 4-二甲氨基吡啶 、 sodium hydroxide 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 (3S,4R)-3-<(1R)-1-<(tert-Butyldimethylsilyl)oxy>ethyl>-4-<(1S)-1-<(2-thioxo-1,3-thiazolidin-3-yl)carbonyl>ethyl>azetidin-2-one
  参考文献：
  名称：

  .beta.-Lactams. 3. Asymmetric total synthesis of new non-natural 1.beta.-methylcarbapenems exhibiting strong antimicrobial activities and stability against human renal dehydropeptidase-I

  摘要：

  Asymmetric synthesis of 11, the precursor to chiral (3R,4R)-3-[(1R)-1-[(tert-butyldimethylsilyl)oxy]ethyl]-4-acetoxyazetidin-2-one (3) was achieved by utilizing a highly diastereoselective aldol-type reaction of acetaldehyde and the chiral tin(II) enolate of 5. Similar diastereoselective alkylations of chiral and achiral tin(II) enolates 13a-d with chiral 3 were also performed to obtain the desired alkylated azetidin-2-ones (17a-d). Compounds 17a,b were successfully converted to new, non-natural 1-beta-methylcarbapenems 1a and 1b, which exhibited strong and wide-ranging antimicrobial activities and excellent stability against human renal dehydropeptidase-I.

  DOI：

  10.1021/jo00041a033
• 作为产物：
  描述：

  4-乙酰氧基氮杂环丁酮 在 三乙胺 、 sodium iodide 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 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：

  通过非对映选择性脱羧立体键合成关键的1β-甲基卡巴培南中间体

  摘要：

  由（3R，4R）-4-乙酰氧基-制备（3S，4S）-3 [（R）-1-（叔丁基二甲基甲硅烷氧基）乙基] -4-[（R）-1-羧乙基] -2-氮杂环丁酮。3 - [（R）-1-吨-butyldimethylsilyloxy）乙基] -2-氮杂环丁酮通过涉及与2,2,5-三甲基-1,3-二恶烷-4,6-二酮耦合的序列，ñ -silylation，溶剂分解甲基熔体的酸部分和立体选择性酸催化的脱羧反应。

  DOI：

  10.1016/0040-4039(94)85197-2

文献信息

• (2R,3R)-3-[(1R)-1-{[tert-Butyl(dimethyl)silyl]oxy}ethyl]-4-oxoazetidin-2-yl Acetate in Zinc- and Samarium-Promoted Substitution Reactions with Methyl 2-Bromopropanoate and Methyl (2-Bromomethyl)prop-2-enoate. Unusual Cleavage of the N1‒C4 Bond in Azetidin-2-one Derivative with Migration of Methoxycarbonyl Group in Synthetic Approaches to Carbapenems and Their Analogs
  作者：Z. R. Valiullina、L. S. Khasanova、N. K. Selezneva、L. V. Spirikhin、Yu. N. Belokon’、M. S. Miftakhov

  DOI：10.1134/s1070428018070096

  日期：2018.7

  l(dimethyl) silyl]oxy}ethyl]-1-(2-methoxy-2-oxoethyl)-4-oxoazetidin-2-yl}-2(RS)-methyl-3-oxopentanoate which underwent fragmentation through cleavage of the N1–C4 bond under the action of sodium bis(trimethylsilyl)-amide in THF at–78°C. The resulting acyclic amide, dimethyl (2R,S,3Z)-2-[(1R)-1-[tert-butyl(dimethyl)-silyl]oxy}ethyl)]-4-methyl-5-oxohept-3-enoylamino}malonate, was smoothly converted

  锌在（2 R，3 R）-3-[（1 R）-1-[叔丁基（二甲基）甲硅烷基]氧基}-乙基] -4-氧杂ze啶-2-基的Barbier型反应中的使用具有卤素衍生物的乙酸乙烯酯导致形成预期的取代产物。标题化合物与由sa粉，催化量的碘和2-溴丙酸甲酯在THF中制备的试剂反应，得到异常取代产物2-（2 S，3 S）-3-[（1 R）-1-[[叔丁基（二甲基）甲硅烷基]氧基}乙基] -4-氧杂氮杂环丁烷-2-基} -2（R，S）-3-氧戊酸甲酯 后者与溴乙酸甲酯烷基化，得到2-（2 S，3 S）-3-[（1 R）-1-[叔丁基（二甲基）甲硅烷基]氧基}乙基] -1-（2-甲基）甲氧基-2-氧乙基）-4-氧杂氮杂环丁烷-2-基} -2（RS）-3-氧戊酸甲酯，在双（三甲基甲硅烷基）-酰胺钠的作用下，通过裂解N 1 -C 4键进行裂解在–78°C下的THF中。生成的无环酰胺二甲基（2 R，S，3
• Shih, David H.; Baker, Florence; Cama, Lovji, Heterocycles, 1984, vol. 21, # 1, p. 29 - 40
  作者：Shih, David H.、Baker, Florence、Cama, Lovji、Christensen, Burton G.

  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.
• An Unusual Stereoselective Decarboxylation: A Key Reaction to an Important Intermediate for Carbapenem Antibiotics
  作者：Woo-Baeg Choi、Hywyn R. O. Churchill、Joseph E. Lynch、R. P. Volante、Paul J. Reider、Ichiro Shinkai、Deborah K. Jones、Dennis C. Liotta

  DOI：10.1021/jo00131a010

  日期：1995.12

  The dramatic difference in reactivity of the two diastereomeric acid esters 4A and 4B during decarboxylation has been thoroughly investigated, The (R) isomer 4A underwent decarboxylation to provide a 94:6 mixture of 5A and 5B at 80 degrees C in 5-6 h. Under the same conditions the (S) isomer 4B did not undergo decarboxylation and with further heating to 120 degrees C gave mainly the ring-opened decomposition product 6 along with unidentified decomposition products, A mechanistic rationale for this unusual reactivity profile is provided.
• Diastereoselective routes to a 1.beta.-methylcarbapenem key intermediate. Scope of ate complex formation between ester enolates and organoboranes and -alanes
  作者：Dean R. Bender、Anthony M. DeMarco、David G. Melillo、Stephen M. Riseman、Ichiro Shinkai

  DOI：10.1021/jo00034a039

  日期：1992.4

  Two diastereoselective syntheses of the 1-beta-methylcarbapenem key intermediate 5 are described. Triethylborane-mediated epimerization of the alpha-methyl diastereomer 4 proceeds with high stereoselectivity to give pure 5 in good yield. Triethylaluminum-mediated methylation of the desmethyl analogue 3 gives 5 with modest stereoselectivity. Low-temperature FT-IR studies of reaction intermediates demonstrated that the epimerization proceeds via an ate complex, while the methylation does not involve ate complex formation. The scope of ate complex formation with trialkylboranes and trialkylalanes was thus more clearly defined, with the IR data providing a rough indication of the extent to which trialkylaluminum ate complexes are less stable than the trialkylborane analogs. The IR studies also provided useful information about enolate aggregation and the effects of cations, amines, HMPA and temperature on ate complex formation.