phenyl N-methyl-3-(p-trifluoromethylphenoxy)-3-phenylpropyl-amine-N-carboxylate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: phenyl N-methyl-3-(p-trifluoromethylphenoxy)-3-phenylpropyl-amine-N-carboxylate
• 英文别名: Phenyl N-methyl-3-(p-trifluoromethylphenoxy)-3-phenylpropylamine-N-carboxylate；phenyl N-methyl-3-(4-trifluoromethyl-phenyloxy)-3-phenyl-propylcarbamate；fluoxetine phenylcarbamate；phenyl N-methyl-N-[3-phenyl-3-[4-(trifluoromethyl)phenoxy]propyl]carbamate
• 化学式: C₂₄H₂₂F₃NO₃
• 分子量: 429.439
• InChiKey: LQZHIQSXNXIAEH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  phenyl N-methyl-3-(p-trifluoromethylphenoxy)-3-phenylpropyl-amine-N-carboxylate 在 甲基氯化镁 、 水 、 氯化铵 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 生成 氟西汀
  参考文献：
  名称：

  [EN] METHOD FOR THE PREPARATION OF N-METHYL-ARYLOXY-PROPANAMINE DERIVATIVES
  [FR] PROCÉDÉ DE PRÉPARATION DE DÉRIVÉS DE N-MÉTHYL-ARYLOXY-PROPANAMINE

  摘要：

  公开号：

  WO2010010412A8
• 作为产物：
  描述：

  3-(4-(三氟甲基)苯氧基)-N,N-二甲基-3-苯基丙-1-胺 、 氯甲酸苯酯 在 三乙胺 作用下， 以 甲苯 为溶剂， 反应 1.0h， 生成 phenyl N-methyl-3-(p-trifluoromethylphenoxy)-3-phenylpropyl-amine-N-carboxylate
  参考文献：
  名称：

  [EN] METHOD FOR THE PREPARATION OF N-METHYL-ARYLOXY-PROPANAMINE DERIVATIVES
  [FR] PROCÉDÉ DE PRÉPARATION DE DÉRIVÉS DE N-MÉTHYL-ARYLOXY-PROPANAMINE

  摘要：

  公开号：

  WO2010010412A8

文献信息

• PROCESS FOR THE PREPARATION OF ARYLOXYPROPYLAMINES
  申请人：MANTEGAZZA Simone

  公开号：US20070270483A1

  公开（公告）日：2007-11-22

  A process for preparation of a compound of formula (I), or a salt thereof, both as individual isomer and as mixtures thereof, wherein each of A and B is independently aryl or heteroaryl optionally substituted with 1 to 4 substituents; and R and R 1 , which can be the same or different, are hydrogen, C 1 -C 6 alkyl or an amino-protecting group; comprising the reaction of a compound (II) wherein A and B are as defined above, with a compound (III) wherein each of R and R 1 is independently C 1 -C 6 alkyl or an amino-protecting group; and X is a leaving group; in the presence of a basic agent; and, if desired the conversion of a compound (I) to another compound (I); and/or, if desired, the separation of an isomeric mixture of a compound (I) into the individual isomers; and/or, if desired, the conversion of a compound (I) to a salt thereof.

  一种制备化合物(I)或其盐的方法，该化合物可以是单体异构体，也可以是它们的混合物，其中A和B分别独立地是芳基或杂环芳基，可选择地取代1到4个取代基；R和R1可以相同也可以不同，是氢、C1-C6烷基或氨基保护基；包括将化合物(II)（其中A和B如上定义）与化合物(III)（其中R和R1分别独立地是C1-C6烷基或氨基保护基；X是一个离去基团）在碱性试剂存在下反应；如有需要，将化合物(I)转化为另一种化合物(I)；和/或如有需要，将化合物(I)的异构混合物分离成单体异构体；和/或如有需要，将化合物(I)转化为其盐。
• N-substituted derivatives of
  申请人：PLIVA Farmaceutska kemijska, Prehrambena i kozmeticka industrija,

  公开号：US05618968A1

  公开（公告）日：1997-04-08

  The invention provides the preparation procedure for N-substituted derivatives of N-methyl-3-(p-trifluoromethylphenoxy)-3 -phenylpropylamine having the general formula (I), where R is hydrogen and the group of the general formula (II), in which R.sub.1 is aryl, alkylaryl and alkyl group with C.sub.1 to C.sub.4 atoms, and n is 0 and 1, and also covers the compounds of the general formula (I), where R is the group of the formula (II), in which R.sub.1 is aryl and alkylaryl group, and n is 0 and 1. According to this invention by condensation of N-substituted derivatives of N-methyl-3-phenyl-3-hydroxypropylamine (XV), where R.sub.1 is benzyl and p-nitrobenzyl group and n is 0, and p-trifluoromethylchlorbenzene (XVI) prepared N-substituted derivatives of N-methyl-3-(p-trifluoromethylphenoxy)-3 -phenylpropylamine (I), where R is the group of the formula (II), in which n and R are the same as in the compound (XV), which by the reaction with chloroformic acid esther (XVII), where R.sub.1 aryl, alkylaryl and alkyl group with C.sub.1 to C.sub.4 atoms, are converted to N-substituted derivatives of N-methyl-3-(p -trifluoromethylphenoxy)-3-phenylpropylamine (I), where R is the group of the formula (II), in which R.sub.1 is the same as in the compound (XVII), and n is 1, from which is prepared the compound of the formula (I), in which R is hydrogen (Fluoxetin), by basic hydrolysis and/or catalytic hydrogenolysis, when R is the group of the formula (II), in which R.sub.1 is benzyl and p-nitrobenzyl group, and n is 0 and 1.

  本发明提供了N-取代N-甲基-3-(对三氟甲基苯氧基)-3-苯基丙胺的制备方法，其具有通式(I)，其中R为氢原子和通式(II)中的基团，其中R1为芳基、烷基芳基和碳原子数为C1到C4的烷基，n为0和1，并且还包括通式(I)的化合物，其中R为通式(II)中的基团，其中R1为芳基和烷基芳基基团，n为0和1。根据本发明，通过N-取代N-甲基-3-苯基-3-羟基丙胺(XV)和p-三氟甲基氯苯(XVI)的缩合反应，制备了N-取代N-甲基-3-(对三氟甲基苯氧基)-3-苯基丙胺(I)，其中R为通式(II)中的基团，其中n和R与化合物(XV)中相同，通过与氯甲酸酯(XVII)反应，其中R1为芳基、烷基芳基和碳原子数为C1到C4的烷基，转化为N-取代N-甲基-3-(对三氟甲基苯氧基)-3-苯基丙胺(I)，其中R为通式(II)中的基团，其中R1与化合物(XVII)中相同且n为1，从而通过碱性水解和/或催化氢解制备出通式(I)中R为氢原子(Fluoxetin)的化合物，当R为通式(II)中的基团，其中R1为芳基和p-硝基苯基基团，n为0和1。
• N-subtituted derivatives of N-methyl-3-(p-trifluoromethylphenoxy)-3-phenylpropylamine and the procedure for their preparation
  申请人：PLIVA d.d. ZAGREB

  公开号：EP0617006A1

  公开（公告）日：1994-09-28

  The invention provides the preparation procedure for N-substituted derivatives of N-methyl-3-(p-trifluoromethylphenoxy)-3-phenylpropylamine having the general formula (I), where R is hydrogen, benzyl and p-nitrobenzyl group, and n is 0, and where R is aryl, alkylaril and alkyl group with C₁ to C₄ atoms, and n is 1, and also covers the compounds of the general formula (I), where R is aryl and alkylaril group, and n is 0 and 1. According to this invention by condensation of N-substituted derivatives of N-methyl-3-phenyl-3-hydroxypropylamine (XV), where R is benzyl and p-nitrobenzyl group and n is 0, and p-trifluoromethylchlorbenzene (XVI) prepared are N-substituted derivatives of N-methyl-3-(p-trifluoromethylphenoxy)-3-phenylpropylamine (I), where n and R are the same as in the compound (XV), which by the reaction with chloroformic acid esther (XVII), where R is aryl, alkylaril and alkyl group with C₁ to C₄ atoms, are converted to N-substituted derivatives of N-methyl-3-(p-trifluoromethylphenoxy)-3-phenylpropylamine (I), where R is the same as in the compound (XVII), and n is 1, from which N-methyl-3-(p-trifluoromethylphenoxy)-3-phenylpropylamine (I) is prepared by basic hydrolysis and/or catalytic hydrogenolysis, when R is benzyl and p-nitrobenzyl group, and n is 0 and 1.

  本发明提供了具有通式(I)的N-甲基-3-(对三氟甲基苯氧基)-3-苯基丙胺的N-取代衍生物的制备步骤，其中R为氢、苄基和对硝基苄基、且 n 为 0，以及 R 为芳基、烷基芳烷基和具有 C₁ 至 C₄ 原子的烷基且 n 为 1 的通式(I)化合物，还包括 R 为芳基和烷基芳烷基且 n 为 0 和 1 的通式(I)化合物。 根据本发明，通过缩合 N-甲基-3-苯基-3-羟基丙胺的 N-取代衍生物 (XV)，其中 R 为苄基和对硝基苄基，n 为 0、和对三氟甲基氯苯(XVI)制备的是 N-甲基-3-(对三氟甲基苯氧基)-3-苯基丙胺(I)的 N-取代衍生物，其中 n 和 R 与化合物(XV)中的相同，通过与氯仿酸酯(XVII)反应、其中 R 为芳基、烷基芳基和具有 C₁ 至 C₄ 原子的烷基，通过与氯甲酸酯 (XVII) 反应，转化为 N-甲基-3-(对三氟甲基苯氧基)-3-苯基丙胺 (I) 的 N-取代衍生物，其中 R 与化合物 (XVII) 中的相同、当 R 为苄基和对硝基苄基，且 n 为 0 和 1 时，N-甲基-3-(对三氟甲基苯氧基)-3-苯基丙胺(I)由其通过碱性水解和/或催化氢化裂解制备。
• A process for the preparation of aryloxypropylamines
  申请人：Dipharma Francis S.r.l.

  公开号：EP1857435A2

  公开（公告）日：2007-11-21

  A process for the preparation of a compound of formula (I), or a salt thereof, both as the as individual isomer and as mixtures thereof, wherein each of A and B is independently aryl or heteroaryl optionally substituted with 1 to 4 substituents; and R and R1, which can be the same or different, are hydrogen, C1-C6 alkyl or an amino-protecting group; comprising the reaction of a compound (II) wherein A and B are as defined above, with a compound (III) wherein each of R and R1 is independently C1-C6 alkyl or an amino-protecting group; and X is a leaving group; in the presence of a basic agent; and, if desired the conversion of a compound (I) to another compound (I); and/or, if desired, the separation of an isomeric mixture of a compound (I) into the individual isomers; and/or, if desired, the conversion of a compound (I) to a salt thereof.

  一种制备式（I）化合物或其盐的工艺，包括单个异构体和混合物、 其中 A 和 B 各自独立地为被 1 至 4 个取代基任选取代的芳基或杂芳基；以及 R 和 R1（可以相同或不同）为氢、C1-C6 烷基或氨基保护基团；包括化合物 (II) 的反应 其中 A 和 B 如上定义，与化合物 (III) 反应 其中 R 和 R1 分别独立地为 C1-C6 烷基或氨基保护基；X 为离去基团；在碱性剂存在下；如果需要，将化合物 (I) 转化为另一种化合物 (I)；和/或，如果需要，将化合物 (I) 的异构混合物分离为单个异构体；和/或，如果需要，将化合物 (I) 转化为其盐。
• N-Substituted derivatives of N-methyl-3-(p-trifluoromethylphenoxy)-3-phenylpropylamine and procedure for their preparation
  申请人：PLIVA farmaceutska, kemijska, prehrambena i kozmeticka industrija, dionicko drustvo

  公开号：EP0617006B1

  公开（公告）日：1998-05-06