332347-69-0

Basic information

• Product Name: Benzeneacetic acid, 3-ethoxy-4-(ethoxycarbonyl)-, ethyl ester
• Synonyms: Benzeneacetic acid, 3-ethoxy-4-(ethoxycarbonyl)-, ethyl ester
• CAS NO: 332347-69-0
• Molecular Formula: C₁₅H₂₀O₅
• Molecular Weight: 280.3163
• Mol File: 332347-69-0.mol

Chemical Properties

• Boiling Point: 386.5°C at 760 mmHg
• Flash Point: 168.9°C
• Appearance: /
• Density: 1.105g/cm³
• Vapor Pressure: 3.53E-06mmHg at 25°C
• Refractive Index: 1.499
• CAS DataBase Reference: Benzeneacetic acid, 3-ethoxy-4-(ethoxycarbonyl)-, ethyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: Benzeneacetic acid, 3-ethoxy-4-(ethoxycarbonyl)-, ethyl ester(332347-69-0)
• EPA Substance Registry System: Benzeneacetic acid, 3-ethoxy-4-(ethoxycarbonyl)-, ethyl ester(332347-69-0)

Safety Data

• Hazardous Substances Data: 332347-69-0(Hazardous Substances Data)

Usage

InChI:InChI=1/C15H20O5/c1-4-18-13-9-11(10-14(16)19-5-2)7-8-12(13)15(17)20-6-3/h7-9H,4-6,10H2,1-3H3

Upstream product

• 64-17-5 ethanol 
• 99470-01-6 ethyl 4-cyanomethyl-2-ethoxy-benzoate 
• 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 
• 99469-99-5 2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid 
• 220438-80-2 2-ethoxy-[4-(carboxymethyl)]benzoic acid 
• 74-96-4 ethyl bromide 
• 22446-38-4 ethyl 3-hydroxyphenylacetate 
• 621-37-4 m-hydroxyphenylacetic acid 
• 201230-82-2 carbon monoxide 

Downstream Products

• 219922-30-2 ethyl 2-ethoxy-4-<2-<<2-cycloheptyl-1-<2-(1-piperidinyl)phenyl>ethyl>amino>-2-oxoethyl>-benzoate 
• 107362-10-7 ethyl 2-ethoxy-4-<2-<<2-cyclohexyl-1-<2-(1-piperidinyl)phenyl>ethyl>amino>-2-oxoethyl>-benzoate 
• 219922-29-9 ethyl 2-ethoxy-4-<2-<<2-cyclopentyl-1-<2-(1-piperidinyl)phenyl>ethyl>amino>-2-oxoethyl>-benzoate 
• 219922-26-6 ethyl 2-ethoxy-4-<2-<<1-<2-(1-piperidinyl)phenyl>heptyl>amino>-2-oxoethyl>-benzoate 
• 219922-28-8 ethyl 2-ethoxy-4-<2-<<2-cyclobutyl-1-<2-(1-piperidinyl)phenyl>ethyl>amino>-2-oxoethyl>-benzoate 
• 219922-25-5 ethyl 2-ethoxy-4-<2-<<1-<2-(1-piperidinyl)phenyl>hexyl>amino>-2-oxoethyl>-benzoate 
• 107362-11-8 ethyl 2-ethoxy-4-<2-<<2-phenyl-1-<2-(1-piperidinyl)phenyl>ethyl>amino>-2-oxoethyl>-benzoate 
• 219922-27-7 ethyl 2-ethoxy-4-<2-<<2-cyclopropyl-1-<2-(1-piperidinyl)phenyl>ethyl>amino>-2-oxoethyl>-benzoate 
• 219922-24-4 ethyl 2-ethoxy-4-<2-<<3-methyl-1-<2-(1-piperidinyl)phenyl>3-buten-1-yl>amino>-2-oxoethyl>-benzoate 
• 219922-23-3 ethyl 2-ethoxy-4-<2-<<1-<2-(1-piperidinyl)phenyl>4-penten-1-yl>amino>-2-oxoethyl>-benzoate 
• 219922-22-2 ethyl 2-ethoxy-4-<2-<<1-<2-(1-piperidinyl)phenyl>pentyl>amino>-2-oxoethyl>-benzoate 
• 219922-19-7 ethyl 2-ethoxy-4-<2-<<1-<5-chloro-2-(1-piperidinyl)phenyl>propyl>amino>-2-oxoethyl>-benzoate 
• 99469-91-7 ethyl 2-ethoxy-4-[N-(α-phenyl-2-piperidino-benzyl)aminocarbonylmethyl]-benzoate 

Relevant articles and documents

Preparation method of repaglinide key intermediate

The invention discloses a preparation method of a repaglinide key intermediate (I). The preparation method comprises the following steps: reacting ethyl 4-methyl-2-ethoxybenzoate (II) with carbon monoxide and alcohol under the conditions of a catalyst and an oxidant, and selectively hydrolyzing reactants to obtain an intermediate (I). The preparation method is simple, efficient, mild in condition,good in reproducibility, high in yield and suitable for industrial production.

A new route for the synthesis of the repaglinide key intermediate 3-ethoxy-4-ethoxycarbonylphenylacetic acid

A new method is described for manufacturing 3-ethoxy-4-ethoxycarbonylphenylacetic acid, which is a key intermediate of the antidiabetic drug repaglinide, starting from 3-hydroxyphenylacetic acid and involving esterification, formylation, oxidation, etherification and selective hydrolysis. The effect of reaction temperature, time, solvent and substrate ratios on the yield were studied in detail and the optimal conditions are presented in the paper. The new method makes the scale-up operation easier and the environmental problems are fewer. The impurities in the intermediate of the new route were also determined. Characterisation of the product and intermediates involved was achieved by FTIR, 1H NMR, 13C NMR, HRMS and DSC.

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 ETHYL 3-ETHOXY-4-ETHOXYCARBONYL-PHENYLACETATE

The present invention relates to a process for the preparation of ethyl 3-ethoxy-4-ethoxycarbonyl-phenylacetate having formula 1. Ethyl 3-ethoxy-4-ethoxycarbonyl-phenylacetate (1) is an important key intermediate for the synthesis of repaglinide (2) an or

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.