(3S,4R)-3-<(R)-1-(t-Butyldimethylsilyloxy)ethyl>-4-<(R)-1-((S)-4-benzyl-2-oxazolidone-3-carbonyl)ethyl>-2-azetidinone | 109715-77-7

• 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-benzyl-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)-4-benzyloxazolin-4-one；(S)-3-((R)-2-(3-((R)-1-(t-butyldimethylsilyloxy)ethyl)-4-oxoazetidine-2-yl)propanoyl)-4-benzyloxazolidine-2-one；(3S,4R)-3-[(R)-1-(t-Butyldimethylsilyloxy)ethyl]-4-[(R)-1-((S)-4-benzyl-2-oxazolidone-3-carbonyl)ethyl]-2-azetidinone；(4S)-4-benzyl-3-[(2R)-2-[(2R,3S)-3-[(1R)-1-[tert-butyl(dimethyl)silyl]oxyethyl]-4-oxoazetidin-2-yl]propanoyl]-1,3-oxazolidin-2-one
• CAS: 109715-77-7
• 化学式: C₂₄H₃₆N₂O₅Si
• 分子量: 460.646
• InChiKey: WMTLNCRBQHKKSJ-SCQOQHIRSA-N

物化性质

• 沸点：
  592.2±15.0 °C(Predicted)
• 密度：
  1.129±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.74
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 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-benzyl-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：

  L-苯丙氨醇 在 四氯化钛 、 potassium carbonate 、 三乙胺 、 zinc(II) chloride 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 6.5h， 生成 (3S,4R)-3-<(R)-1-(t-Butyldimethylsilyloxy)ethyl>-4-<(R)-1-((S)-4-benzyl-2-oxazolidone-3-carbonyl)ethyl>-2-azetidinone
  参考文献：
  名称：

  Method for manufacturing stereoselective preparation of 4-BMA using a chiral auxiliary and chiral auxiliary

  摘要：

  本发明涉及一种制备(3R,4S)-3-[[[R]-1'-叔丁基二甲基硅氧基]乙基]-4-[(R)-1''-羧乙基]-2-氮杂环己酮（β-甲基氮杂环己酮; 4-BMA）的过程，该化合物是头孢内酯和青霉素类抗生素合成的关键中间体。具体来说，本发明涉及一种包括首先从廉价的L-苯丙氨醇制备手性辅助体，然后在工业温和条件下高产率高选择性地制备4-BMA的过程。

  公开号：

  US20110144326A1

文献信息

• Method for manufacturing stereoselective preparation of 4-bma using a chiral auxiliary and chiral auxiliary
  申请人：Savior Lifetec Corporation

  公开号：EP2345645A1

  公开（公告）日：2011-07-20

  The present invention relates to a process for preparing (3R,4S)-3-[[[R]-1 ' -t-butyldimethylsilyloxy ]ethyl]-4-[(R)-1 "-carboxyethyl]-2-azetidinone (beta- methylazetidin-2-one; 4-BMA), a key intermediate for the synthesis of carbapenem and penem antibiotics. Specifically, the present invention relates to a process comprising first, the preparation of a chiral auxiliary from cheap L-Phenylalaninol, and then the preparation of 4-BMA in high yield and high selectivity, under industrially mild condition.

  本发明涉及一种制备(3R,4S)-3-[[[R]-1'-t-丁基二甲基硅氧基]乙基]-4-[(R)-1"-羧乙基]-2-氮杂环己酮（β-甲基氮杂环己酮；4-BMA）的工艺，该化合物是头孢菌素和青霉素类抗生素合成的关键中间体。具体而言，本发明涉及一种工艺，首先从廉价的L-苯丙氨醇制备手性辅助基，然后在工业温和条件下高产率高选择性地制备4-BMA。
• 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。
• 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：——
• Addition of amino amides to vinyl vicinal tricarbonyls. Formation of tricyclic 3-azadethiacephams
  作者：Harry H. Wasserman、Susan L. Henke、Eiji Nakanishi、Gayle Schulte

  DOI：10.1021/jo00035a019

  日期：1992.4

  Amino amides react as trinucleophiles with vinyl vicinal tricarbonyl esters. Reaction of the primary amino group takes place at the beta-position of the alpha,beta-unsaturated ketone along with addition to the central carbonyl group. In a third-stage reaction, the amide residue adds to the iminium ion formed from the intermediate carbinolamine. The resulting product is a bicyclic or tricyclic (acylamino)pyrrolidone carboxylate. A novel tricyclic 3-azadethiacepham of biological interest has been prepared using this reaction.
• 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：——