(3S,4R)-3-<(R)-1-(t-Butyldimethylsilyloxy)ethyl>-4-<(R)-1-((S)-4-isopropyl-2-oxazolidone-3-carbonyl)ethyl>-2-azetidinone | 255837-99-1

• 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,4R)-3-<(R)-1-(t-Butyldimethylsilyloxy)ethyl>-4-<(R)-1-((S)-4-isopropyl-2-oxazolidone-3-carbonyl)ethyl>-2-azetidinone
• 英文别名: 3-{(2R)-2-[(3S,4R)-3-[(1R)-1-tert-butyldimethylsilyloxyethyl]-2-oxoazetidin-4-yl]propionyl}-(4S)-isopropyloxazolin-4-one；(3S,4R)-3-[(R)-1-(t-Butyldimethylsilyloxy)ethyl]-4-[(R)-1-((S)-4-isopropyl-2-oxazolidone-3-carbonyl)ethyl]-2-azetidinone；(4S)-3-[(2R)-2-[(2R,3S)-3-[(1R)-1-[tert-butyl(dimethyl)silyl]oxyethyl]-4-oxoazetidin-2-yl]propanoyl]-4-propan-2-yl-1,3-oxazolidin-2-one
• CAS: 255837-99-1
• 化学式: C₂₀H₃₆N₂O₅Si
• 分子量: 412.602
• InChiKey: WGRCRQMJDXNSSU-OXGONZEZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.15
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  84.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3S,4R)-3-<(R)-1-(t-Butyldimethylsilyloxy)ethyl>-4-<(R)-1-((S)-4-isopropyl-2-oxazolidone-3-carbonyl)ethyl>-2-azetidinone 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 、 乙醚 、 乙酸乙酯 为溶剂， 反应 4.0h， 生成 methyl (2R)-2-[(2S,3S)-3-{(1R)-1-(t-butyldimethylsilyloxy)ethyl}-4-oxoazetidin-2-yl]propionate
  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：

  (S)-4-异丙基-2-唑烷酮 在 正丁基锂 、 锌 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 0.5h， 生成 (3S,4R)-3-<(R)-1-(t-Butyldimethylsilyloxy)ethyl>-4-<(R)-1-((S)-4-isopropyl-2-oxazolidone-3-carbonyl)ethyl>-2-azetidinone
  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

文献信息

• Process for the preparation of 4-substituted azetidinone derivatives
  申请人：Takasago International Corporation

  公开号：US06340751B1

  公开（公告）日：2002-01-22

  Disclosed is a process for the preparation of a 4-substituted azetidinone derivative, which comprises reacting an azetidinone derivative and an amide compound in the presence of a magnesium compound such as those represented by the following formulas (II): and (IV): represented by the following formula (III): MgR5R6  (III) wherein R5 represents a C1-12 alkyl group, a C2-5 alkenyl group, a 5- to 8-membered alicyclic group which may be substituted by a lower C1-4 alkyl group, a phenyl group which may be substituted by a lower C1-4 alkyl group, a lower C1-4 alkoxy group or a halogen atom or a benzyl group which may be substituted by a lower C1-4 alkyl group, a lower C1-4 alkoxy group or a halogen atom, and R6 represents a halogen atom, a methanesulfonyloxy group, a benzenesulfonyloxy group, a p-toluenesulfonyloxy group, a trifluoromethanesulfonyloxy group, an acetoxy group which may be substituted by a halogen atom or a cyano group or an OR7 group (R7 representing a lower C1-4 alkyl group, a substituted or unsubstituted phenyl group or a substituted or unsubstituted benzyl group). The process provides an industrially excellent process for the preparation of a 4-substituted azetidinone derivative which permits the selective preparation of an intermediate for the synthesis of a carbapenem antibacterial agent having a desired 1-&bgr;′ configuration.

  揭示了一种制备4-取代氮杂环己酮衍生物的过程，包括在镁化合物的存在下，反应氮杂环己酮衍生物和酰胺化合物，所述镁化合物可由以下公式（II）和（IV）所表示：MgR5R6  （III）其中R5代表C1-12烷基，C2-5烯基，5-至8-成员的脂环基，该脂环基可以被低C1-4烷基取代，苯基，该苯基可以被低C1-4烷基，低C1-4烷氧基或卤素原子取代，苄基，该苄基可以被低C1-4烷基，低C1-4烷氧基或卤素原子取代；R6代表卤素原子，甲磺酰氧基，苯磺酰氧基，对甲苯磺酰氧基，三氟甲磺酰氧基，乙酰氧基，该乙酰氧基可以被卤素原子或氰基或OR7基（R7代表低C1-4烷基，取代或未取代的苯基或取代或未取代的苄基）取代。该过程提供了一种在工业上优秀的制备4-取代氮杂环己酮衍生物的过程，可允许选择性制备用于合成具有所需1-β'构型的碳青霉烯类抗菌剂的中间体。
• Lewis acid mediated condensation of chiral imide enolates. A general approach to the synthesis of chiral carbapenem precursors
  作者：Lelia M. Fuentes、I. Shinkai、T. N. Salzmann

  DOI：10.1021/ja00275a083

  日期：1986.7
• A highly stereoselective synthesis of a key intermediate of 1β-methylcarbapenems employing the reformatsky reaction of 3-(2-bromopropionyl)-2-oxazolidone derivatives
  作者：Yoshio Ito、Shiro Terashima

  DOI：10.1016/s0040-4039(00)96930-2

  日期：——
• 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.