(2-苯甲酰氨基-苯基)-乙酸 | 106737-75-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: (2-苯甲酰氨基-苯基)-乙酸
• 英文名称: (2-benzoylamino-phenyl)-acetic acid
• 英文别名: (2-Benzoylamino-phenyl)-essigsaeure；2-Benzamino-phenylessigsaeure；2-(2-Benzamidophenyl)acetic acid
• CAS: 106737-75-1
• 化学式: C₁₅H₁₃NO₃
• mdl: MFCD17501742
• 分子量: 255.273
• InChiKey: KASKMAZRPJTKKY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.066
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2-苯甲酰氨基-苯基)-乙酸 在 soda lime 作用下， 生成 2-苯基吲哚
  参考文献：
  名称：

  Murakoshi, Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan, 1959, vol. 79, p. 76,79

  摘要：

  DOI：
• 作为产物：
  描述：

  N-benzoyl-N-phenyl-O-(acetyl)hydroxylamine 在 水 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 生成 (2-苯甲酰氨基-苯基)-乙酸
  参考文献：
  名称：

  Synthetic applications of -Aryl- -acyl hydroxymic acids. A convenient route to 3-substituted -Benzoyl oxindoles

  摘要：

  The enol silylethers of N-acyloxybenzanilides undergo smooth rearrangement to afford o-amino-benzoyl-phenylacetic acids and thence to oxinodoles by dehydration.

  DOI：

  10.1016/s0040-4039(00)78815-0

文献信息

• Method of synthesizing diclofenac sodium
  申请人：FUDAN UNIVERSITY

  公开号：US10662145B2

  公开（公告）日：2020-05-26

  The invention relates to the chemical synthesis of pharmaceutical API, and specifically to a method of synthesizing diclofenac sodium, which is a kind of nonsteroidal anti-inflammatory drug for relieving pain. The method includes: nitrating phenylacetate to prepare o-nitrophenylacetate (2); hydrogenating o-nitrophenylacetate (2) to prepare o-aminophenylacetate (3); amidating an amino group of o-aminophenylacetate (3) to obtain 2-(2-benzoylaminophenyl) acetate (4); 2-(2-benzoylaminophenyl) acetate (4) reacting with thionyl chloride to prepare a chloroimine intermediate, and then condensing the intermediate of chloroimine with 2,6-dichlorophenol using an inorganic base to prepare (E)-methyl-2-(2-((2,6-dichlorophenoxy)(phenyl)methyleneamino) phenyl ester (5); subjecting (E)-methyl-2-(2-((2,6-dichlorophenoxy)(phenyl)methyleneamino) phenyl ester (5) to Chapman rearrangement to afford methyl 2-(2-(N-(2,6-dichlorophenyl)benzoylamino)phenyl) ester (6); and hydrolyzing methyl 2-(2-(N-(2,6-dichlorophenyl)benzoylamino)phenyl) ester (6) to provide the target compound as of diclofenac sodium API. The overall yield is up to 67% based on methyl phenylacetate.

  本发明涉及药物原料药的化学合成，具体涉及一种合成双氯芬酸钠的方法，双氯芬酸钠是一种用于缓解疼痛的非甾体类消炎药。该方法包括硝化苯乙酸，制备邻硝基苯乙酸酯（2）；氢化邻硝基苯乙酸酯（2），制备邻氨基苯乙酸酯（3）；酰胺化邻氨基苯乙酸酯（3）的氨基，得到 2-（2-苯甲酰基氨基苯基）乙酸酯（4）；2-(2-苯甲酰基氨基苯基)乙酸酯(4)与亚硫酰氯反应，制备氯亚胺中间体，然后用无机碱将氯亚胺中间体与 2,6-二氯苯酚缩合，制备(E)-甲基-2-(2-((2,6-二氯苯氧基)(苯基)亚甲基氨基)苯基酯(5)将(E)-甲基-2-(2-((2,6-二氯苯氧基)(苯基)亚甲基氨基)苯基酯(5)进行查普曼重排，得到甲基-2-(2-(N-(2,6-二氯苯基)苯甲酰氨基)苯基)酯(6)并水解 2-(2-(N-(2,6-二氯苯基)苯甲酰氨基)苯基)甲基酯 (6)，得到双氯芬酸钠原料药的目标化合物。以苯乙酸甲酯为基准，总产率高达 67%。
• v. Braun; Bartsch, Chemische Berichte, 1912, vol. 45, p. 3388
  作者：v. Braun、Bartsch

  DOI：——

  日期：——
• Neber, Chemische Berichte, 1922, vol. 55, p. 839
  作者：Neber

  DOI：——

  日期：——
• de Martiis, Annali di Chimica, 1957, vol. 47, p. 1238,1240
  作者：de Martiis

  DOI：——

  日期：——
• METHOD OF SYNTHESIZING DICLOFENAC SODIUM
  申请人：FUDAN UNIVERSITY

  公开号：US20200055811A1

  公开（公告）日：2020-02-20

  The invention relates to the chemical synthesis of pharmaceutical API, and specifically to a method of synthesizing diclofenac sodium, which is a kind of nonsteroidal anti-inflammatory drug for relieving pain. The method includes: nitrating phenylacetate to prepare o-nitrophenylacetate (2); hydrogenating o-nitrophenylacetate (2) to prepare o-aminophenylacetate (3); amidating an amino group of o-aminophenylacetate (3) to obtain 2-(2-benzoylaminophenyl) acetate (4); 2-(2-benzoylaminophenyl) acetate (4) reacting with thionyl chloride to prepare a chloroimine intermediate, and then condensing the intermediate of chloroimine with 2,6-dichlorophenol using an inorganic base to prepare (E)-methyl-2-(2-((2,6-dichlorophenoxy)(phenyl)methyleneamino) phenyl ester (5); subjecting (E)-methyl-2-(2-((2,6-dichlorophenoxy)(phenyl)methyleneamino) phenyl ester (5) to Chapman rearrangement to afford methyl 2-(2-(N-(2,6-dichlorophenyl)benzoylamino)phenyl) ester (6); and hydrolyzing methyl 2-(2-(N-(2,6-dichlorophenyl)benzoylamino)phenyl) ester (6) to provide the target compound as of diclofenac sodium API. The overall yield is up to 67% based on methyl phenylacetate.