4-aminophenylalanine ethyl ester

• 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: 4-aminophenylalanine ethyl ester
• 英文别名: DL-(p-aminophenyl)alanine ethyl ester；4-Amino-phenylalanin-aethylester；Ethyl 2-amino-3-(4-aminophenyl)propanoate
• 化学式: C₁₁H₁₆N₂O₂
• 分子量: 208.26
• InChiKey: RAXLHWJKWFXAAE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  78.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氨基-3-(4-硝基苯基)丙酸乙酯 在 盐酸 、 titanium(III) chloride 作用下， 以 水 、 乙腈 为溶剂， 反应 1.0h， 以99%的产率得到4-aminophenylalanine ethyl ester
  参考文献：
  名称：

  Applications of TiCl₃ as a Diagnostic Reagent for the Detection of Nitro- and N-Oxide-Containing Compounds as Potentially Mutagenic Impurities Using Ultrahigh-Performance Liquid Chromatography Coupled with High-Resolution Mass Spectrometry

  摘要：

  The ICH has strict guidelines for limiting the presence of potentially mutagenic impurities (PMIs) in marketed drugs. Therefore, it is important to fully characterize and quantitate all possible PMIs that could arise during the process of synthesizing and developing a drug. Two important and prevalent examples of PMIs are compounds containing N-oxide and nitro functional groups. TiCl3 derivatization is an established method for determining the presence or absence of N-oxide metabolites by reduction to the corresponding amine. In this study, we demonstrate a novel application of TiCl3 reduction combined with high-resolution UHPLC/HRMS to analyze PMIs. The results indicate that a variety of N-oxide- and nitro-containing compounds can be readily characterized by this facile platform method. In addition, we show that this chemical derivatization method can be utilized to enhance the ionization of nitro-containing compounds for LC/MS analysis.

  DOI：

  10.1021/acs.oprd.5b00312

文献信息

• Nucleophilic substitution on 4-hydroxymethylanilines under ‘neutral’ conditions via aza quinone methide intermediate
  作者：Hiroyasu Takahashi、Nobuyuki Kashiwa、Hisayoshi Kobayashi、Yuichi Hashimoto、Kazuo Nagasawa

  DOI：10.1016/s0040-4039(02)01198-x

  日期：2002.8

  Substitution reaction of 4-hydroxymethylaniline derivatives with resonance-stabilized carbon nucleophiles and an acid-labile nucleophile, including β-ketoester, 1,3-diketone, α-nitroester, and silylenolether, proceeded efficiently upon heating at 80°C in a neutral solvent system. The reaction was successfully applied to the synthesis of 4-aminophenylalanine.

  在中性溶剂中于80°C加热后，4-羟甲基苯胺衍生物与共振稳定的碳亲核试剂和酸不稳定的亲核试剂（包括β-酮酸酯，1,3-二酮，α-硝基酯和甲硅烷基醚）的取代反应有效地进行。系统。该反应成功地用于合成4-氨基苯丙氨酸。
• 2-(Ethoxycarbonylmethyl)-1H-naphtho[1,8-de]-1,2,3-triazine anion: a new glycine enolate equivalent
  作者：R Anilkumar、Sosale Chandrasekhar、Malayalam Sridhar

  DOI：10.1016/s0040-4039(00)01115-1

  日期：2000.8

  The titled triazine can be alkylated with LDA and a variety of alkyl halides: subsequent reduction with aluminium amalgam cleaves the naphthotriazine moiety to afford substituted α amino acids in excellent overall yields; the sequence defines a novel methodology that can be applied under non-acidic and largely non-aqueous conditions.

  可以将标题的三嗪用LDA和各种烷基卤化物进行烷基化：随后用铝汞齐还原，将萘并三嗪部分裂解，以优异的总收率得到取代的α氨基酸。该序列定义了一种可以在非酸性和很大程度上非水性条件下应用的新颖方法。
• Efficient Synthesis of <font>α</font>-Substituted Amino Acid Ester: Alkylation and Hydrogenation Removal of Schiff's Base Protecting Group
  作者：Aslam M. Ansari、Sydney O. Ugwu

  DOI：10.1080/00397910802138611

  日期：2008.6.27

  Abstract A general and efficient synthetic route to α-amino acids by alkylation of the sodium salt of Schiff base ester 1 has been described previously. The α-substituted ethyl glycinates 4a–g are prepared in excellent yield by a two-step sequence involving regioselective alkylation of the anionic glycine synthon 2 with various alkyl halides, followed by purification of the alkylated Schiff base on

  摘要 先前已经描述了通过席夫碱酯 1 的钠盐的烷基化来合成 α-氨基酸的通用且有效的路线。α-取代的甘氨酸乙酯 4a-g 通过两步序列以极好的收率制备，包括用各种卤代烷对阴离子甘氨酸合成子 2 进行区域选择性烷基化，然后在 Florisil 上纯化烷基化的希夫碱，并通过催化氢解进行裂解。侧链上的可还原基团可以减少或保留，这取决于所用的去保护方法。方案一
• Applications of TiCl₃ as a Diagnostic Reagent for the Detection of Nitro- and <i>N</i>-Oxide-Containing Compounds as Potentially Mutagenic Impurities Using Ultrahigh-Performance Liquid Chromatography Coupled with High-Resolution Mass Spectrometry
  作者：Rong-Sheng Yang、Adam Beard、Huaming Sheng、Li-Kang Zhang、Roy Helmy

  DOI：10.1021/acs.oprd.5b00312

  日期：2016.1.15

  The ICH has strict guidelines for limiting the presence of potentially mutagenic impurities (PMIs) in marketed drugs. Therefore, it is important to fully characterize and quantitate all possible PMIs that could arise during the process of synthesizing and developing a drug. Two important and prevalent examples of PMIs are compounds containing N-oxide and nitro functional groups. TiCl3 derivatization is an established method for determining the presence or absence of N-oxide metabolites by reduction to the corresponding amine. In this study, we demonstrate a novel application of TiCl3 reduction combined with high-resolution UHPLC/HRMS to analyze PMIs. The results indicate that a variety of N-oxide- and nitro-containing compounds can be readily characterized by this facile platform method. In addition, we show that this chemical derivatization method can be utilized to enhance the ionization of nitro-containing compounds for LC/MS analysis.