718-08-1

Basic information

• Product Name: 3-OXO-4-PHENYL-BUTYRIC ACID ETHYL ESTER
• Synonyms: 3-OXO-4-PHENYL-BUTYRIC ACID ETHYL ESTER;3-keto-4-phenyl-butyric acid ethyl ester;ethyl 3-oxo-4-phenylbutanoate;ethyl 3-oxo-4-phenyl-butanoate;4-Phenyl-3-oxobutanoic acid ethyl ester;Ethyl 4-phenylacetoacetate;Benzenebutanoic acid, b-oxo-, ethyl ester;b-Oxo-benzenebutanoic acid ethyl ester
• CAS NO: 718-08-1
• Molecular Formula: C₁₂H₁₄O₃
• Molecular Weight: 206.24
• Mol File: 718-08-1.mol

Chemical Properties

• Boiling Point: 290℃
• Flash Point: 124℃
• Appearance: /
• Density: 1.091
• Vapor Pressure: 0.00209mmHg at 25°C
• Refractive Index: 1.054-1.059
• Storage Temp.: Inert atmosphere,Room Temperature
• Solubility: Chloroform (Slightly), DMSO (Slightly), Methanol (Sparingly)
• PKA: 10.49±0.46(Predicted)
• CAS DataBase Reference: 3-OXO-4-PHENYL-BUTYRIC ACID ETHYL ESTER(CAS DataBase Reference)
• NIST Chemistry Reference: 3-OXO-4-PHENYL-BUTYRIC ACID ETHYL ESTER(718-08-1)
• EPA Substance Registry System: 3-OXO-4-PHENYL-BUTYRIC ACID ETHYL ESTER(718-08-1)

Safety Data

• Statements: 36/37/38
• Safety Statements: 26-36/37/39
• Hazardous Substances Data: 718-08-1(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
3-OXO-4-PHENYL-BUTYRIC ACID ETHYL ESTER is used as a synthetic intermediate for the preparation of pyrazolone derivatives, which are known for their antiprion properties. These compounds have the potential to inhibit the formation of prion proteins, which are associated with neurodegenerative diseases such as Creutzfeldt-Jakob disease and bovine spongiform encephalopathy (BSE), commonly known as mad cow disease.
Used in Biochemical Research:
In the field of biochemical research, 3-OXO-4-PHENYL-BUTYRIC ACID ETHYL ESTER is used as a precursor for the synthesis of pyrrolinylaminopyrimidine analogs. These analogs act as inhibitors of AP-1 and NF-κB mediated gene expression, which are crucial for regulating various cellular processes, including inflammation, immune response, and cell proliferation. By inhibiting these pathways, pyrrolinylaminopyrimidine analogs can potentially be used to develop treatments for various diseases and conditions, such as cancer and inflammatory disorders.
Used in Chemical Synthesis:
3-OXO-4-PHENYL-BUTYRIC ACID ETHYL ESTER is also utilized in the chemical synthesis industry as a versatile building block for the creation of various organic compounds. Its reactivity and functional groups make it suitable for use in a wide range of chemical reactions, allowing for the development of new and innovative products.

Synthesis Reference(s)

Journal of Medicinal Chemistry, 44, p. 78, 2001 DOI: 10.1021/jm001034kChemical and Pharmaceutical Bulletin, 30, p. 2440, 1982 DOI: 10.1248/cpb.30.2440

Synthesis

The synthesis of Ethyl 3-oxo-4-phenylbutanoate is as follows:Monoethyl monopotassium malonate (12.9 g, 2.3 equivalents) was mixed with tetrahydrofuran (200 ml), and the mixture was cooled to 5°C. Triethylamine (8.2 g, 2.5 equivalents) and magnesium chloride (8.62 g, 2.8 equivalents) were added, and the mixture was stirred at 5 to 20°C for 3 hours. The reaction mixture was cooled to 5°C. Phenacyl chloride (5 g, 32 mmol, 1 equivalent) was gradually added, and the mixture was stirred at 5 to 20°C for 63 hours. The mixture was cooled to 5°C, and 1 N hydrochloric acid (30 ml) was added. Tetrahydrofuran was evaporated away under reduced pressure, and extraction was carried out with ethyl acetate (50 ml). The organic layer was washed with 1 N hydrochloric acid (30 ml), water (10 ml), saturated aqueous solution of sodium hydrogencarbonate (30 ml) and water (10 ml) in order. The solvent was evaporated away under reduced pressure to obtain the Ethyl 3-oxo-4-phenylbutanoate as a pale yellow oil (5.82 g, yield: 86 %).

InChI:InChI=1/C12H14O3/c1-2-15-12(14)9-11(13)8-10-6-4-3-5-7-10/h3-7H,2,8-9H2,1H3

Upstream product

• 1071-46-1 hydrogen ethyl malonate 
• 103-80-0 phenylacetyl chloride 
• 64-17-5 ethanol 
• 66696-84-2 5-(1-hydroxy-2-phenylethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione 
• 140-29-4 phenylacetonitrile 
• 105-36-2 ethyl bromoacetate 
• 95092-10-7 N-methoxy-N-methyl-2-phenylacetamide 
• 141-78-6 ethyl acetate 
• 623-73-4 diazoacetic acid ethyl ester 
• 122-78-1 phenylacetaldehyde 
• 412019-21-7 ethyl 2-acetyl-3-oxo-4-phenylbutanoate 
• 60-29-7 diethyl ether 
• 7664-41-7 ammonia 
• 103-82-2 phenylacetic acid 

Downstream Products

• 855161-56-7 4-benzyl-5-hydroxy-7-methyl-coumarin 
• 176519-53-2 ethyl 2-isopropyl-3-oxo-4-phenylbutanoate 
• 102473-93-8 2,4-dioxo-3,6-diphenyl-cyclohexanecarboxylic acid ethyl ester 
• 855161-63-6 4-benzyl-5,7-dihydroxy-coumarin 
• 102657-43-2 6-(3,4-dimethoxy-phenyl)-2,4-dioxo-3-phenyl-cyclohexanecarboxylic acid ethyl ester 
• 75523-28-3 5-benzyl-1,2-dihydropyrazol-3-one 
• 132-86-5 1,3-dihydroxynaphthalene 
• 135608-75-2 benzyl carbamate 
• 58190-83-3 2-phenylacetyl-hexanoic acid ethyl ester 
• 76595-36-3 ethyl 2-acetoxy-3-oxo-4-phenylbutanoate 
• 412323-19-4 2-(4-nitro-benzyl)-4-phenyl-acetoacetic acid ethyl ester 
• 916248-70-9 diethyl (phenylacetyl)succinate 
• 861067-78-9 2-phenethyl-4-phenyl-acetoacetic acid ethyl ester 
• 856118-83-7 ethyl 2-benzyl-4-phenyl-1H-pyrrole-3-carboxylate 

Relevant articles and documents

Discovery of pyrrolo[2,3-d]pyrimidine derivatives as potent Axl inhibitors: Design, synthesis and biological evaluation

Axl has emerged as an attractive target for cancer therapy due to its strong correlation with tumor growth, metastasis, poor survival, and drug resistance. Herein, we report the design, synthesis and structure-activity relationship (SAR) investigation of a series of pyrrolo[2,3-d]pyrimidine derivatives as new Axl inhibitors. Among them, the most promising compound 13b showed high enzymatic and cellular Axl potencies. Furthermore, 13b possessed preferable pharmacokinetic properties and displayed promising therapeutic effect in BaF3/TEL-Axl xenograft tumor model. Compound 13b may serve as a lead compound for new antitumor drug discovery.

Non-metal Lewis acid-catalyzed cross-Claisen condensation for β-keto esters

In this work, we disclose a new catalytic and highly chemoselective cross-Claisen condensation of esters. In the presence of TBSNTf2 as a non-metal Lewis acid, various esters can undergo cross-Claisen condensation to form β-keto esters which are important building blocks. Compared with the traditional Claisen condensation, this process, employing silyl ketene acetals (SKAs) as carbonic nucleophiles to achieve cross-Claisen condensation, requires mild conditions and has good tolerance of functional groups. This journal is

Deconstructing Noncovalent Kelch-like ECH-Associated Protein 1 (Keap1) Inhibitors into Fragments to Reconstruct New Potent Compounds

Targeting the protein-protein interaction (PPI) between nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) is a potential therapeutic strategy to control diseases involving oxidative stress. Here, six classes of known small-molecule Keap1-Nrf2 PPI inhibitors were dissected into 77 fragments in a fragment-based deconstruction reconstruction (FBDR) study and tested in four orthogonal assays. This gave 17 fragment hits of which six were shown by X-ray crystallography to bind in the Keap1 Kelch binding pocket. Two hits were merged into compound 8 with a 220-380-fold stronger affinity (Ki = 16 μM) relative to the parent fragments. Systematic optimization resulted in several novel analogues with Ki values of 0.04-0.5 μM, binding modes determined by X-ray crystallography, and enhanced microsomal stability. This demonstrates how FBDR can be used to find new fragment hits, elucidate important ligand-protein interactions, and identify new potent inhibitors of the Keap1-Nrf2 PPI.

Desymmetrization of meso-dicarbonatecyclohexene with β-Hydrazino carboxylic esters via a Pd-catalyzed allylic substitution cascade

The desymmetrization of meso-dicarbonatecyclohexene with β-hydrazino carboxylic esters has been achieved via a RuPHOX/Pd-catalyzed allylic substitution cascade for the construction of chiral hexahydrocinnoline derivatives with high performance. Mechanistic studies reveal that the reaction exploits a pathway different from that of our previous work and that the first nitrogen nucleophilic process is the rate-determining step. The protocol could be conducted on a gram scale without any loss of catalytic behavior, and the corresponding chiral hexahydrocinnolines can undergo diverse transformations.

General [4 + 1] Cyclization Approach to Access 2,2-Disubstituted Tetrahydrofurans Enabled by Electrophilic Bifunctional Peroxides

A general [4 + 1] cyclization reaction of carbonyl nucleophiles with 2-iodomethylallyl peroxides, which function as unique electrophilic oxygen synthons, for the synthesis of a broad range of 2,2-disubstituted tetrahydrofurans is achieved under operationally simple conditions. The unprecedented asymmetric version of such reaction is also realized via chiral auxiliary-assisted cyclization, thus providing a distinct approach to access chiral tetrahydrofurans with high diastereoselectivities. The new method can be applied to the synthesis of core structure of posaconazole drug.

2-Arylthio-5-iodo pyrimidine derivatives as non-nucleoside HBV polymerase inhibitors

In this study, a series of 2-arylthio-5-iodo pyrimidine derivatives, as non-nucleoside hepatitis B virus inhibitors, were evaluated and firstly reported as potential anti-HBV agents. To probe the mechanism of active agents, DHBV polymerase was isolated and a non-radioisotopic assay was established for measuring HBV polymerase. The biological results demonstrated that 2-arylthio-5-iodo pyrimidine derivatives targeted HBV polymerase. In addition, pharmacophore models were constructed for future optimization of lead compounds. Further study will be performed for the development of non-nucleoside anti-HBV agents.

NRF 2 ACTIVATOR

Provided are compounds of Formula I, or pharmaceutically acceptable salts thereof, which are activators of nuclear factor erythroid 2 (NF-E2) -related factor 2 (Nrf2) and are useful to treat diseases caused by oxidative stress, such as neurodegenerative diseases or inflammation. Also provided are methods for their use and production.

Five Roads That Converge at the Cyclic Peroxy-Criegee Intermediates: BF3-Catalyzed Synthesis of β-Hydroperoxy-β-peroxylactones

We have discovered synthetic access to β-hydroperoxy-β-peroxylactones via BF3-catalyzed cyclizations of a variety of acyclic precursors, β-ketoesters and their silyl enol ethers, alkyl enol ethers, enol acetates, and cyclic acetals, with H2O2. Strikingly, independent of the choice of starting material, these reactions converge at the same β-hydroperoxy-β-peroxylactone products, i.e., the peroxy analogues of the previously elusive cyclic Criegee intermediate of the Baeyer-Villiger reaction. Computed thermodynamic parameters for the formation of the β-hydroperoxy-β-peroxylactones from silyl enol ethers, enol acetates, and cyclic acetals confirm that the β-peroxylactones indeed correspond to a deep energy minimum that connects a variety of the interconverting oxygen-rich species at this combined potential energy surface. The target β-hydroperoxy-β-peroxylactones were synthesized from β-ketoesters, and their silyl enol ethers, alkyl enol ethers, enol acetates, and cyclic acetals were obtained in 30-96% yields. These reactions proceed under mild conditions and open synthetic access to a broad selection of β-hydroperoxy-β-peroxylactones that are formed selectively even in those cases when alternative oxidation pathways can be expected. These β-peroxylactones are stable and can be useful for further synthetic transformations.

PYRIDO-AZAHETERECYDIC COMPOUND AND PREPARATION METHOD AND USE THEREOF

The present invention discloses a pyrido-azacyclic compound represented by formula I, an isomer thereof, a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof, a preparation process thereof and a composition comprising the compound, and a use thereof as a multi-target protein kinase inhibitor in the preparation of a medicament for the treatment of diseases that are associated with protein kinase, especially c-Met, such as cancer and the like. The compound represented by formula I has potent inhibitory activity on tumor cells with overexpression of c-Met kinase, can effectively target c-Met-mediated signaling pathway, and can be used in the treatment of diseases such as cancer and the like that is caused by the overexpression of c-Met kinase.

Practical and Efficient Synthesis of Polyaryl(hetaryl)-Substituted Cyclohexenones and Salicylates

A new efficient method was developed for the synthesis of triaryl-substituted cyclohexenones and salicylates. The method is based on the Robinson annulation of readily available keto esters and chalcones, followed by the aromatization of the cyclohexenone moiety. The aromatization can be accomplished either by reaction with bromine in boiling chloroform or bromination with copper(II) bromide in ethanol followed by treatment with pyridine or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). The new synthetic method was also implemented in a one-pot protocol, which in some cases resulted in higher yields of the final product compared to those obtained in the stepwise synthesis.