3-(4-trifluoromethyl-phenylamino)-pentanoic acid methyl ester | 749921-33-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 3-(4-trifluoromethyl-phenylamino)-pentanoic acid methyl ester
• 英文别名: methyl (R)-3-[4-(trifluoromethyl)phenylamino]-pentanoate；methyl 3-(R)-3-(4-trifluoromethylphenylamino)pentanoate；methyl (3R)-3-(4-trifluoromethylphenylamino)pentanoate；methyl (3R)-3-(4-trifluoromethylphenylamino)-pentanoate；methyl (3R)-3-[4-(trifluoromethyl)anilino]pentanoate
• CAS: 749921-33-3
• 化学式: C₁₃H₁₆F₃NO₂
• 分子量: 275.271
• InChiKey: IMFUUTDACQERTQ-SNVBAGLBSA-N

物化性质

• 沸点：
  338.0±42.0 °C(Predicted)
• 密度：
  1.203±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-(4-trifluoromethyl-phenylamino)-pentanoic acid methyl ester 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 1.17h， 以58%的产率得到methyl (R)-N-[3-(4-trifluoromethyl-phenylamino)pentanoyl]carbamate
  参考文献：
  名称：

  [EN] METHOD FOR PRODUCING AN OPTICALLY ACTIVE TETRAHYDROQUINOLINE
  [FR] PROCEDE DE PRODUCTION D'UNE TETRAHYDROQUINOLINE ACTIVE SUR LE PLAN OPTIQUE

  摘要：

  公开号：

  WO2004074255A3
• 作为产物：
  描述：

  methyl 3-(4-trifluoromethylphenylamino)-2-pentenoate 在 C₂H₈N⁽¹⁺⁾*2C₃₈H₂₈O₄P₂*5Cl^(1-)*2Ru⁽²⁺⁾ 氢气 作用下， 以 异丙醇 为溶剂， 95.0 ℃ 、5.0 MPa 条件下， 反应 2.0h， 以85%的产率得到3-(4-trifluoromethyl-phenylamino)-pentanoic acid methyl ester
  参考文献：
  名称：

  [EN] METHOD FOR PRODUCING AN OPTICALLY ACTIVE TETRAHYDROQUINOLINE
  [FR] PROCEDE DE PRODUCTION D'UNE TETRAHYDROQUINOLINE ACTIVE SUR LE PLAN OPTIQUE

  摘要：

  公开号：

  WO2004074255A3

文献信息

• Method for producing (R) -3- [4- (trifluoromethyl) phenylamino] -pentanoic acid amide derivative
  申请人：KANEKA CORPORATION

  公开号：US20040199005A1

  公开（公告）日：2004-10-07

  The present invention provides a method for easily producing an (R)-3-[4-(trifluoromethyl)phenylamino]-pentanoic acid amide derivative useful for an intermediate for pharmaceutical products, particularly an inhibitor of a cholesteryl ester transfer protein (CETP) from easily available raw materials. In the present invention, (S)-N-[4-(trifluoromethyl)phenyl]-3-hydroxypentanoic acid amide prepared from easily available raw materials leads a production of (R)-4-ethyl-1-[4-(trifluoromethyl)phenyl]-2-azetidinone to give (R)-3-[4-(trifluoromethyl)phenylamino]-pentanoic acid amide. Furthermore, (R)-4-ethyl-1-[4-(trifluoromethyl)phenyl]-2-azetidinone is reacted with a carbamic acid ester to give an (R)-3-[4-(trifluoromethyl)phenylamino]-pentanoic acid amide derivative.

  本发明提供了一种从易获得的原料中轻松生产(R)-3-[4-(三氟甲基)苯基氨基]-戊酸酰胺衍生物的方法，该衍生物可用作制药产品中间体，特别是一种胆固醇酯转移蛋白(CETP)抑制剂的中间体。在本发明中，从易获得的原料制备的(S)-N-[4-(三氟甲基)苯基]-3-羟基戊酸酰胺导致(R)-4-乙基-1-[4-(三氟甲基)苯基]-2-氮杂环己酮的生产，从而得到(R)-3-[4-(三氟甲基)苯基氨基]-戊酸酰胺。此外，(R)-4-乙基-1-[4-(三氟甲基)苯基]-2-氮杂环己酮与一种碳酸酯反应，形成(R)-3-[4-(三氟甲基)苯基氨基]-戊酸酰胺衍生物。
• Method for producing an optically active tetrahydroquinoline
  申请人：Moroi Takashi

  公开号：US20060122225A1

  公开（公告）日：2006-06-08

  The present invention provides an industrially advantageous production method of optically active tetrahydroquinolines of formula (1), which comprises: 1) a step of reacting a β-ketoester of formula (2) with an amine of formula (3) to produce an enaminoester of formula (4); 2) a step of subjecting the enaminoester of formula (4) above obtained in 1) to asymmetric hydrogenation to produce an optically active β-amino acid derivative of formula (5); 3) a step of amidating the optically active β-amino acid derivative (5) above obtained in 2) to produce an amide of formula (6); 4) a step of alkoxycarbonylating the amide of formula (6) above obtained in 3) to produce a compound of formula (7); and 5) a step of subjecting the compound of formula (7) above to cyclization to produce the optically active tetrahydroquinoline of formula (1).

  本发明提供了一种工业上优势的光学活性四氢喹啉的生产方法，其中包括以下步骤：1）将化学式（2）的β-酮酸酯与化学式（3）的胺反应，生成化学式（4）的烯胺酸酯；2）将步骤1）中获得的化学式（4）的烯胺酸酯进行不对称氢化，生成光学活性的化学式（5）的β-氨基酸衍生物；3）将步骤2）中获得的光学活性的化学式（5）的β-氨基酸衍生物进行酰胺化，生成化学式（6）的酰胺；4）将步骤3）中获得的化学式（6）的酰胺进行烷氧羰基化，生成化学式（7）的化合物；5）将步骤4）中获得的化学式（7）的化合物进行环化，生成光学活性的化学式（1）的四氢喹啉。
• Asymmetric reductive amination of keto acid derivatives for producing amino acid derivatives
  申请人：Matsumura Kazuhiko

  公开号：US20070142443A1

  公开（公告）日：2007-06-21

  The present invention relates to a process for producing amino acid derivatives such as optically active β-amino acid in short steps with good yield and high optical purity, which comprises reacting a keto acid of the formula (1): wherein R 1 is hydrogen, an optionally substituted hydrocarbon, etc.; R 2 is a spacer; and R 3 is an optionally substituted alkoxy, etc., or a salt thereof, with ammonia or an amine or a salt thereof in the presence of a chiral catalyst and in the presence or absence of an acid and/or a fluorine-containing alcohol, to give an amino acid derivative of the formula (2): wherein Q is a group formed by removing one hydrogen atom from ammonia or an amine; X′ is an acid and/or a fluorine-containing alcohol; and b is 0 or 1.

  本发明涉及一种生产氨基酸衍生物的方法，例如短步骤中产生具有良好收率和高光学纯度的光学活性β-氨基酸。该方法包括在手性催化剂的存在下，与氨或胺或其盐一起在酸和/或含氟醇的存在或缺席下反应式（1）的酮酸： 其中，R1是氢、可选取代的碳氢化合物等；R2是间隔物；R3是可选取代的烷氧基等，或其盐，以得到式（2）的氨基酸衍生物： 其中，Q是从氨或胺中去除一个氢原子形成的基团；X'是酸和/或含氟醇；b为0或1。
• METHOD FOR PRODUCING AN OPTICALLY ACTIVE TETRAHYDROQUINOLINE
  申请人：Moroi Takashi

  公开号：US20100036149A1

  公开（公告）日：2010-02-11

  The present invention provides an industrially advantageous production method of optically active tetrahydroquinolines of formula (1), which comprises: 1) a step of reacting a β-ketoester of formula (2) with an amine of formula (3) to produce an enaminoester of formula (4); 2) a step of subjecting the enaminoester of formula (4) above obtained in 1) to asymmetric hydrogenation to produce an optically active β-amino acid derivative of formula (5); 3) a step of amidating the optically active β-amino acid derivative (5) above obtained in 2) to produce an amide of formula (6); 4) a step of alkoxycarbonylating the amide of formula (6) above obtained in 3) to produce a compound of formula (7); and 5) a step of subjecting the compound of formula (7) above to cyclization to produce the optically active tetrahydroquinoline of formula (1).

  本发明提供了一种工业上优越的光学活性四氢喹啉的生产方法，其包括以下步骤： 1）用式（2）的β-酮酸酯与式（3）的胺反应生成式（4）的烯酰胺酯的步骤； 2）将式（1）中获得的式（4）的烯酰胺酯进行不对称氢化，生成光学活性的β-氨基酸衍生物的步骤； 3）将步骤2）中获得的光学活性β-氨基酸衍生物（5）进行酰胺化，生成式（6）的酰胺的步骤； 4）将步骤3）中获得的酰胺（6）进行烷氧羰基化，生成式（7）的化合物的步骤； 5）将步骤4）中获得的式（7）的化合物进行环化，生成式（1）的光学活性四氢喹啉的步骤。
• Method for producing (R)-3-[4-(trifluoromethyl) phenylamino]-pentanoic acid amide derivative
  申请人：Pfizer Inc.

  公开号：US07223859B2

  公开（公告）日：2007-05-29

  The present invention provides a method for easily producing an (R)-3-[4-(trifluoromethyl)phenylamino]-pentanoic acid amide derivative useful for an intermediate for pharmaceutical products, particularly an inhibitor of a cholesteryl ester transfer protein (CETP) from easily available raw materials. In the present invention, (S)-N-[4-(trifluoromethyl)phenyl]-3-hydroxypentanoic acid amide prepared from easily available raw materials leads a production of (R)-4-ethyl-1-[4-(trifluoromethyl)phenyl]-2-azetidinone to give (R)-3-[4-(trifluoromethyl)phenylamino]-pentanoic acid amide. Furthermore, (R)-4-ethyl-1-[4-(trifluoromethyl)phenyl]-2-azetidinone is reacted with a carbamic acid ester to give an (R)-3-[4-(trifluoromethyl)phenylamino]-pentanoic acid amide derivative.

  本发明提供了一种从易得的原料中制备(R)-3-[4-(三氟甲基)苯氨基]-戊酸酰胺衍生物的方法，该衍生物是一种用于制药产品中间体的有用化合物，特别是胆固醇酯转移蛋白（CETP）抑制剂。在本发明中，从易得的原料制备的(S)-N-[4-(三氟甲基)苯基]-3-羟基戊酸酰胺导致(R)-4-乙基-1-[4-(三氟甲基)苯基]-2-氮杂环己酮的产生，从而形成(R)-3-[4-(三氟甲基)苯氨基]-戊酸酰胺。此外，(R)-4-乙基-1-[4-(三氟甲基)苯基]-2-氮杂环己酮与一种氨基甲酸酯反应，形成(R)-3-[4-(三氟甲基)苯氨基]-戊酸酰胺衍生物。