220438-80-2

Basic information

• Product Name: (4-Carboxy-3-ethoxy)phenyl Acetic Acid (Repaglinide Impurity)
• Synonyms: 4-(carboxyMethyl)-3-ethoxybenzoic acid;Repaglinide EP IMpurity A;4-(CarboxyMethyl)-2-ethoxybenzoic acid;(4-Carboxy-3-ethoxy)phenyl Acetic Acid
• CAS NO: 220438-80-2
• Molecular Formula: C₁₁H₁₂O₅
• Molecular Weight: 224.20998
• Product Categories: Impurities;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 220438-80-2.mol

Chemical Properties

• Melting Point: 140-142?C
• Boiling Point: 428.1±35.0 °C(Predicted)
• Appearance: /
• Density: 1.319±0.06 g/cm3(Predicted)
• Storage Temp.: -20°C Freezer
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 3.96±0.10(Predicted)
• CAS DataBase Reference: (4-Carboxy-3-ethoxy)phenyl Acetic Acid (Repaglinide Impurity)(CAS DataBase Reference)
• NIST Chemistry Reference: (4-Carboxy-3-ethoxy)phenyl Acetic Acid (Repaglinide Impurity)(220438-80-2)
• EPA Substance Registry System: (4-Carboxy-3-ethoxy)phenyl Acetic Acid (Repaglinide Impurity)(220438-80-2)

Safety Data

• Hazardous Substances Data: 220438-80-2(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(4-Carboxy-3-ethoxy)phenyl Acetic Acid (Repaglinide Impurity) is used as a reference material for quality control and assurance in the manufacturing process of Repaglinide. Its presence is monitored and controlled to ensure the purity and safety of the final drug product.
Additionally, understanding the properties and effects of this impurity can contribute to the optimization of the synthesis process, potentially leading to improved efficiency and reduced impurity levels in the final product. This can be crucial for maintaining the therapeutic efficacy and safety profile of Repaglinide, which is used for the treatment of type 2 diabetes.

InChI:InChI=1S/C11H12O5/c1-2-16-9-5-7(6-10(12)13)3-4-8(9)11(14)15/h3-5H,2,6H2,1H3,(H,12,13)(H,14,15)

Upstream product

• 50-85-1 2-hydroxy-p-toluic acid 
• 88709-17-5 ethyl 2-ethoxy-4-methyl-benzoate 
• 110017-07-7 ethyl 4-bromomethyl-2-ethoxy-benzoate 
• 99470-01-6 ethyl 4-cyanomethyl-2-ethoxy-benzoate 
• 99469-99-5 2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid 
• 124-38-9 carbon dioxide 
• 1379370-52-1 4-chloromethyl-2-ethoxychlorobenzene 
• 503834-19-3 2-(3-ethoxy-4-(methoxycarbonyl)phenyl)acetic acid 

Downstream Products

• 332347-69-0 ethyl 2-ethoxy-4-ethoxycarbonylmethyl-benzoate 
• 1803084-80-1 C₂₇H₃₆N₂O₄ 

Relevant articles and documents

Two d10 metal–organic frameworks based on a novel semi-rigid aromatic biscarboxylate ligand: Syntheses, structures and luminescent properties

Two new d10 metal–organic frameworks based on a novel semi-rigid aromatic biscarboxylate ligand, namely, [Zn (RGAA)(BPY)1/2] (1) and [Cd5(μ3-OH)2(RGAA)4] (2) [H2RGAA = 4-(carboxymethyl)-2-ethoxybenzoic acid, BPY = 4,4′-bipyridine], have been synthesized by the hydrothermal reaction, and characterized by Fourier transform-infrared, elemental analyses, X-ray single-crystal diffraction, powder X-ray diffraction and thermogravimetric analyses. Complex 1 displays a three-dimensional (3D) network with a (2,3,4)-connected (6?3.8?2.10)2(6?3)2(8) topology, while complex 2 exhibits a 3D framework with a (3,10)-connected (3.4.5)2(3?4.4?6.5?18.6?14.7?2.8) topology. The luminescent properties of compounds 1 and 2 have been investigated in detail, where the emission maxima are 464 and 349 nm, respectively.

Preparation, Characterization and Crystal Structures of a Key Intermediate, and a Significant Impurity, in the Synthesis of Repaglinide

Abstract: The crystal structure of 2-(3-ethoxy-4-(methoxycarbonyl)phenyl) acetic acid (RGA), an important intermediate in the preparation of Repaglinide, has been carried out. Hydrogen bonds between the carboxylate groups link the molecules into dimers wh

Preparation method of 3-ethoxy-4-carbozylbenzoic acid

The invention discloses a preparation method of 3-ethoxy-4-carbozylbenzoic acid. The preparation method includes: taking dihalide (IV) as a starting raw material, reacting with metal magnesium to prepare a di-Grignard reagent (V), allowing the di-Grignard

Synthesis of Repaglinide Congeners

This report describes a synthesis of two potent impurities of repaglinide, benzyl repaglinide 1 and repaglinide isomer 2, from commercially available raw materials: 2-fluoro benzonitrile, (S)-3-methyl-1-[2-(piperidin-1-yl)phenyl]butylamine (5), and 3-ethoxy-[4-(ethoxycarbonyl)phenyl]acetic acid (7). These impurities are the crucial components in determining the quality of the drug substance, repaglinide, during its manufacturing.

Process for the preparation of 3-ethoxy-4-(alkoxy carbonyl)-phenyl acetic acid. (an intermediate of repaglinide)

The present invention relates to an improved and convenient process for the preparation of 3-Ethoxy-4-(alkoxy carbonyl)-phenyl acetic acid, which can be represented by formula (Ia) where R1 represents ethyl or methyl. Specifically the present invention relates to an improved process for the preparation of compound of formula (Ia), which is the key intermediate for Repaglinide of formula (I), by the process, which involves non-hazardous raw materials with an easy handling, and cost effective process

Repaglinide and related hypoglycemic benzoic acid derivatives

The structure-activity relationships in two series of hypoglycemic benzoic acid derivatives (5, 6) were investigated. Series 5 resulted from meglitinide (3) when the 2-methoxy was replaced by an alkyleneimino residue. Maximum activity was observed with the cis-3,5-dimethylpiperidino (5h) and the octamethyleneimino (5l) residues. Series 6 resulted from the meglitinide analogon 4 bearing an inversed amido function when the 2-methoxy, the 5- fluoro, and the α-methyl residue were replaced by a 2-piperidino, a 5- hydrogen, and a larger α-alkyl residue, respectively. An alkoxy residue ortho to the carboxy group further increased activity and duration of action in the rat. The most active racemic compound, 6al (R4 = isobutyl; R = ethoxy), turned out to be 12 times more active than the sulfonylurea (SU) glibenclamide (1). Activity was found to reside predominantly in the (S)- enantiomers. Compared with the SUs 1 and 2 (glimepiride), the most active enantiomer, (S)-6al (AG-EE 623 ZW; repaglinide; ED50 = 10 μg/kg po), is 25 and 18 times more active. Repaglinide turned out to be a useful therapeutic for type 2 diabetic patients; approval was granted recently by the FDA and the EMEA. From investigations on the pharmacophoric groups in compounds of type 5 and 6, it was concluded that in addition to the two already known - the acidic group (COOH; S02NH) and the amidic spacer (CONH; NHCO) - the ortho residue R1 (alkyleneimino; alkoxy; oxo) must be regarded as a third one. A general pharmacophore model suitable for hypoglycemic benzoic acid derivatives, SUs, and sulfonamides is proposed (Figure 6). Furthermore, from superpositions of low-energy conformations (LECs) of 1, 2, and (S)-6al, it was concluded that a common binding conformation (LEC II; Figure 10B) may exist and that differences in binding to the SU receptor and in the mechanism of insulin release between repaglinide and the two SUs may be due to specific hydrophobic differences.