2-(2-甲基-2-丙基)-4-氧代-3-氮杂环丁基乙酸酯 | 650625-21-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 中文名称: 2-(2-甲基-2-丙基)-4-氧代-3-氮杂环丁基乙酸酯
• 英文名称: (2S,3R)-2-tert-butyl-4-oxoazetidin-3-yl acetate
• 英文别名: (+)-cis-(3R,4S)-3-acetoxy-4-(1,1-dimethylethyl)-2-azetidinone；[(2S,3R)-2-tert-butyl-4-oxoazetidin-3-yl] acetate
• CAS: 650625-21-1
• 化学式: C₉H₁₅NO₃
• 分子量: 185.223
• InChiKey: POIBROBCVZRHMY-RNFRBKRXSA-N

物化性质

• 沸点：
  305.8±35.0 °C(Predicted)
• 密度：
  1.09±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(2-甲基-2-丙基)-4-氧代-3-氮杂环丁基乙酸酯 在 potassium carbonate 作用下， 以 甲醇 为溶剂， 以29.7 g的产率得到(3R,4S)-4-tert-butyl-3-hydroxyazetidin-2-one
  参考文献：
  名称：

  Enzymatic preparation of (3R)-cis-3-acetyloxy-4-(1,1-dimethylethyl)-2-azetidinone: a side-chain synthon for an orally active taxane

  摘要：

  The chiral intermediate (3R)-cis-3-acetyloxy-4-(I,I-dimethylethyl)-2-azetidinone 2 was prepared for the semi-synthesis of the new taxane 5, an orally active anticancer compound. The enantioselective enzymatic hydrolysis of cis-3-acetyloxy-4-(1,1-dimethylethyl)-2-azetidinone I to the corresponding undesired (S)-alcohol 3 and unreacted desired 2 was carried out using immobilized lipase PS-30 or BMS lipase. Reaction yields of >48% and enantiomeric excesses of >99%, were obtained for the desired 2. Acetoxy beta-lactam 2 was converted to hydroxy beta-lactam 4 for use in the semisynthesis of 5. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2003.09.019
• 作为产物：
  描述：

  在 ammonium cerium(IV) nitrate 、 三乙胺 作用下， 以 phosphate buffer 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 6.0h， 生成 2-(2-甲基-2-丙基)-4-氧代-3-氮杂环丁基乙酸酯
  参考文献：
  名称：

  Arthrobacter sp.: a lipase of choice for the kinetic resolution of racemic arylazetidinone precursors of taxanoid side chains

  摘要：

  The native strain of Arthrobacter sp. (MTCC 5125) bearing a lipase has been found to be the most effective in the kinetic resolution of racemic arylazetidinones for producing cis-(3R,4S)-3-acetoxy-1-(4-methoxyphenyl)-4-phenyl-2-azetidinone, cis-(3R,4R)-3acetoxy-1-(4-methoxyphenyl)-4-(2-furanyl)-2-azetidinone, cis-(3R,4R)-3-acetoxy-1-(4-methoxyphenyl)-4-(2-thienyl)-2-azetidinone, and cis-3-acetoxy-4-(t-butyl)-2-azetidinone products. The resolved compounds, which were obtained in high enantiopurity are important intermediates of amino acid side chains of paclitaxel as well as a new generation of taxanoids. The use of co-solvents dramatically improved the resolution efficacy of the lipase. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2007.04.031

文献信息

• [EN] STEREOSELECTIVE HYDROLYSIS FOR THE RESOLUTION OF RACEMIC MIXTURES OF (+/-) -CIS-S-ACETOXY-L- (4-METHOXYPHENYL) -4- (2-FURYL) -2-AZETIDINONE, (+/-) -CIS-S-ACETOXY-L- (4-METHOXYPHENYL) -4- (2-THIENYL) -2-AZETIDINONE, OR<br/>[FR] HYDROLYSE STÉREOSÉLECTIVE POUR LA RÉSOLUTION DE MÉLANGES RACÉMIQUES À BASE DE (±) -CIS-S-ACÉTOXY-1- (4-MÉTHOXYPHÉNYL) -4- (2-FURYL) -2-AZÉTIDINONE, DE (±) -CIS-S-ACÉTOXY-1- (4-MÉTHOXYPHENYL) -4- (2-THIÉNYL) -2-AZÉTIDINONE, OU DE (±)-CIS-3-ACÉTOXY-4-(
  申请人：COUNCIL SCIENT IND RES

  公开号：WO2009118750A1

  公开（公告）日：2009-10-01

  The present invention provides a stereoselective enzymatic process for the resolution of a mixture of (±)-cis-3-acetoxy-1-(4-methoxyphenyl)-4-(2-furanyl)-2- azetidinone, (±)-cis-3-acetoxy-1-(4-methoxyphenyl)-4-(2-thiophenyl)-2-azetidinone or (±)-cis-3-acetoxy-4-(1,1-dimethylethyl)-2-azetidinone into their optically pure forms by using a lipase enzyme. The invention discloses the use of a native lipase enzyme Arthrobacter simplex (MTCC 5125) in a highly efficient resolution process for the separation of two enantiomers of (±)-c/s-3-acetoxy-1-(4-methoxyphenyl)-4- (2-furanyl)-2-azetidinone, (±)-c/s-3-acetoxy-1-(4-methoxyphenyl)-4-(2-thiophenyl)-2- azetidinone and (±)-c/s-3-acetoxy-4-(1,1-dimethylethyl)-2-azetidinone through stereoselective hydrolysis of their acetyl esters in presence of a organic co-solvent.
• Arthrobacter sp.: a lipase of choice for the kinetic resolution of racemic arylazetidinone precursors of taxanoid side chains
  作者：Naveen Anand、Munish Kapoor、Khursheed Ahmad、Surrinder Koul、Rajinder Parshad、Kuldip S. Manhas、Rattan L. Sharma、Ghulam N. Qazi、Subhash C. Taneja

  DOI：10.1016/j.tetasy.2007.04.031

  日期：2007.5

  The native strain of Arthrobacter sp. (MTCC 5125) bearing a lipase has been found to be the most effective in the kinetic resolution of racemic arylazetidinones for producing cis-(3R,4S)-3-acetoxy-1-(4-methoxyphenyl)-4-phenyl-2-azetidinone, cis-(3R,4R)-3acetoxy-1-(4-methoxyphenyl)-4-(2-furanyl)-2-azetidinone, cis-(3R,4R)-3-acetoxy-1-(4-methoxyphenyl)-4-(2-thienyl)-2-azetidinone, and cis-3-acetoxy-4-(t-butyl)-2-azetidinone products. The resolved compounds, which were obtained in high enantiopurity are important intermediates of amino acid side chains of paclitaxel as well as a new generation of taxanoids. The use of co-solvents dramatically improved the resolution efficacy of the lipase. (C) 2007 Elsevier Ltd. All rights reserved.
• Enzymatic preparation of (3R)-cis-3-acetyloxy-4-(1,1-dimethylethyl)-2-azetidinone: a side-chain synthon for an orally active taxane
  作者：Ramesh N Patel、Jeffrey Howell、Rama Chidambaram、Serge Benoit、Joydeep Kant

  DOI：10.1016/j.tetasy.2003.09.019

  日期：2003.11

  The chiral intermediate (3R)-cis-3-acetyloxy-4-(I,I-dimethylethyl)-2-azetidinone 2 was prepared for the semi-synthesis of the new taxane 5, an orally active anticancer compound. The enantioselective enzymatic hydrolysis of cis-3-acetyloxy-4-(1,1-dimethylethyl)-2-azetidinone I to the corresponding undesired (S)-alcohol 3 and unreacted desired 2 was carried out using immobilized lipase PS-30 or BMS lipase. Reaction yields of >48% and enantiomeric excesses of >99%, were obtained for the desired 2. Acetoxy beta-lactam 2 was converted to hydroxy beta-lactam 4 for use in the semisynthesis of 5. (C) 2003 Elsevier Ltd. All rights reserved.