6018-41-3

Basic information

• Product Name: Methyl coumalate
• Synonyms: Methyl 2-oxo-2H-pyran-5-carboxylate, Methyl 2-pyrone-5-carboxylate;2-Oxo-2H-pyran-5-carboxylic acid methyl ester;2-Oxopyran-5-carboxylic Acid Acid Methyl Ester;2-Pyrone-5-carboxylic Acid Methyl Ester;Methyl 2-Pyrone-5-carboxylate Coumalic acid methyl ester;2H-Pyran-5-carboxylic acid, 2-oxo-, Methyl ester;Coumalic Acid Methyl Ester 2-Oxopyran-5-carboxylic Acid Methyl Ester Methyl 2-Oxopyran-5-carboxylate 2-Pyrone-5-carboxylic Acid Methyl Ester Methyl 2-Pyrone-5-carboxylate;methyl 6-oxopyran-3-carboxylate
• CAS NO: 6018-41-3
• Molecular Formula: C₇H₆O₄
• Molecular Weight: 154.12
• EINECS: 227-871-1
• Product Categories: Ring Systems;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Heterocycles series;Esters
• Mol File: 6018-41-3.mol

Chemical Properties

• Melting Point: 65-67 °C(lit.)
• Boiling Point: 178-180 °C60 mm Hg(lit.)
• Flash Point: 178-180°C/60mm
• Appearance: WHITE TO TAN POWDER OR CRYSTALS
• Density: 1.1993 (rough estimate)
• Vapor Pressure: 0.00893mmHg at 25°C
• Refractive Index: 1.4300 (estimate)
• Storage Temp.: Inert atmosphere,Room Temperature
• Solubility: Freely soluble in dichloromethane.
• Merck: 14,2557
• BRN: 126301
• CAS DataBase Reference: Methyl coumalate(CAS DataBase Reference)
• NIST Chemistry Reference: Methyl coumalate(6018-41-3)
• EPA Substance Registry System: Methyl coumalate(6018-41-3)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 6018-41-3(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Methyl coumalate is used as a cytotoxic agent for its potential applications in cancer research and treatment, specifically targeting oral squamous cell carcinoma cell line-2.
Used in Chemical Synthesis:
Methyl coumalate is used as a reagent in the Diels-Alder reaction, a widely used method in organic chemistry for the synthesis of various compounds. It reacts with 1,3-butadienes at 100°C to yield tetrahydrocoumarins and 4-methoxycarbonyltricyclo[3.2.1.02,7]octenes, and with cyclohexadiene to afford tetrahydronaphthalene-2-carboxylate. It also undergoes Diels-Alder reaction with unactivated alkenes to afford para-substituted adducts.
Used in Organic Chemistry Research:
Methyl coumalate is used as a reagent in phosphine-catalyzed [4+3] annulation of modified allylic carbonates, a reaction that contributes to the development of new synthetic methods and compounds in organic chemistry.
Used in the Preparation of 7-Carboxyquinolizinium Derivatives:
Methyl coumalate is used in the synthesis of 7-carboxyquinolizinium derivatives, which are important intermediates in the preparation of various pharmaceuticals and organic compounds.

InChI:InChI=1/C7H6O4/c1-10-7(9)5-2-3-6(8)11-4-5/h2-4H,1H3

Upstream product

• 67-56-1 methanol 
• 23090-18-8 2-oxo-2H-pyran-5-carbonyl chloride 
• 500-05-0 2H-pyran-2-one-5-carboxylic acid 
• 7664-93-9 sulfuric acid 
• 186581-53-3 diazomethane 
• 617-48-1 malic acid 
• 77-78-1 dimethyl sulfate 
• 118481-26-8 methyl 8-methoxy-8-vinyl-3-oxo-2-oxabicyclo<2.2.2>oct-5-ene-6-carboxylate 

Downstream Products

• 59033-40-8 1-(3,4-dimethoxy-phenethyl)-6-oxo-1,6-dihydro-pyridine-3-carboxylic acid 
• 872824-55-0 6-oxo-1-phenethyl-1,6-dihydro-pyridine-3-carboxylic acid 
• 64972-00-5 4-anilinomethylene-pentenedioic acid-5-methyl ester 
• 3719-45-7 1-methyl-6-oxo-1,6-dihydro-pyridine-3-carboxylic acid 
• 4332-79-0 1-benzyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid 
• 528-44-9 1,2,4-benzene tricarboxylic acid 
• 42933-07-3 methyl 3-bromo-2-oxo-2H-pyran-5-carboxylate 
• 18069-17-5 2-methylglutaric acid 
• 18263-95-1 3,5-dicarboxylic acid-1-benzoic acid methyl ester 
• 75581-72-5 N-phenyl-5-methoxycarbonyl-3,6-endooxycarbonyl-1,2,3,6-tetrahydrophthalimide 
• 75581-80-5 C₂₆H₂₀N₂O₆ 
• 75581-80-5 C₂₆H₂₀N₂O₆ 
• 130232-32-5 4-Methyl-cyclohexa-1,5-diene-1,4-dicarboxylic acid 4-allyl ester 1-methyl ester 
• 76784-93-5 dimethyl 2-methoxycarbonylmethylterephthalate 

Relevant articles and documents

Diels-Alder reaction of 1-methylcycloprop-2-ene-1-carbonitrile with methyl 2-Oxo-2H-pyran-5-carboxylate

The Diels-Alder reaction of 1-methylcycloprop-2-ene-1-carbonitrile and coumalic acid methyl ester (methyl 2-oxo-2H-pyran-5-carboxylate) gave a 2:1 adduct with endo-syn configuration of both cyclopropane fragments, which was established by X-ray analysis. According to the 1H NMR data, the reaction involves intermediate formation of decarboxylated 1:1 adduct having a cycloheptatriene structure; its isomerization into the corresponding caradiene, followed by addition of the second dienophile molecule, was confirmed by quantum-chemical calculations. Pleiades Publishing, Inc., 2006.

Synthesis method of methyl coumalate

The invention discloses a synthesis method of methyl coumalate. The synthesis method comprises the following steps: adding water-containing sulfuric acid into a kettle, stirring, heating to a temperature of less than 100 DEG C, and adding a pre-prepared saturated malic acid solution in a dropwise manner; carrying out a constant-temperature reaction after the adding, and monitoring the reaction process by using gas chromatography until the malic acid reaction is finished; stopping the stirring, layering, cooling to below 50 DEG C, and separating out a lower layer sulfuric acid aqueous solution;continuously stirring, heating to reflux, and adding a large amount of methanol in a dropwise manner; carrying out a reflux reaction for a certain time, and carrying out gas phase monitoring until coumalic acid disappears; evaporating out most of the solvent to form a slurry in the system, cooling to room temperature, and adding an aqueous solution of an alkaline compound in a dropwise manner toform a large amount of precipitates; and filtering, washing with water, and drying to obtain the methyl coumalate.

Stereoselective construction of a key hydroindole precursor of epidithiodiketopiperazine (ETP) natural products

An asymmetric synthetic strategy for constructing the divergent-synthesis monomer of epidithiodiketopiperazine (ETP) natural products has been successfully developed. The functionalized 2,3,3a,4,7,7a-hexahydroindole scaffold was constructed by a diastereoselective inverse electron-demand Diels-Alder (IEDDA) reaction. This journal is the Partner Organisations 2014.

Homosecoiridoid alkaloids with amino acid units from the flower buds of lonicera japonica

Nine new homosecoiridoid alkaloids, named lonijaposides O-W (1-9), along with 19 known compounds, were isolated from an aqueous extract of the flower buds of Lonicera japonica. Their structures and absolute configurations were determined by spectroscopic data analysis and chemical methods. Lonijaposides O-W have structural features that involve amino acid units sharing the N atom with a pyridinium (1-5) or nicotinic acid (6-9) moiety. The absolute configurations of the amino acid units were determined by oxidation of each pyridinium ring moiety with potassium ferricyanide, hydrolysis of the oxidation product, and Marfey's analysis of the hydrolysate. This procedure was validated by oxidizing and hydrolyzing synthetic model compounds. The phenylalanine units in compounds 4, 5, and 9 have the d-configuration, and the other amino acid units in 1-3 and 6-8 possess the l-configuration. Compounds 1, 4, 6, and 9 and the known compounds 3,4-di-O-caffeoylquinic acid, 3,5-di-O-caffeoylquinic acid, and 5′-O-methyladenosine exhibited antiviral activity against the influenza virus A/Hanfang/359/95 (H3N2) with IC50 values of 3.4-11.6 μM, and 4 inhibited Coxsackie virus B3 replication with an IC50 value of 12.3 μM.

Synthesis, pharmacophores, and mechanism study of pyridin-2(1H)-one derivatives as regulators of translation initiation factor 3A

Twenty-seven 1,5-disubstituted-pyridin-2(1H)-one derivatives were synthesized and evaluated for their anti-cancer and anti-fibrosis activity by A549 and NIH3T3 cell viability assays, respectively. To study the selectivity between the cancer and fibrosis cell lines, pharmacophore models (F 1-F4) were built in advance for compounds with pyridin-2(1H)-one scaffold, which revealed the relationship between the occupation of the aromatic sub-site F4 and potent anti-cancer activity. The relationship between structure and anti-cancer activity for all target compounds is also reported herein: 1-Phenyl-5-((m-tolylamino)methyl) pyridine-2(1H)-one (22) displayed both potency and selectivity (IC50 = 0.13 mM) toward the A549 cell line through the inhibition of translation initiation, especially by eIF3a suppression, and can be treated as a lead for the design of novel eIF3a regulators and anti-lung cancer agents. A series of pyridin-2(1H)-one derivatives were synthesized. Elucidation of their pharmacophores and mechanism of action suggested that structures with F 4 occupation displayed more selective anti-cancer than anti-fibrosis activity and that they interrupt the initiation phase of translation by acting on the eukaryotic translation initiation factor 3, subunit A.

Claisen condensation of N-methylpyrrolidinone and α-chloronicotinic esters

Reaction between α-halo-nicotinic esters and a nucleophilic source such as the N-methylpyrrolidin-2-one (NMP) gave unexpected results. The presence of the halide on the pyridine gave a very interesting migration reaction. Extension to 6-methylnicotinic ester derivatives lead to an unexpected carbanion condensation.

A PROCESS FOR THE PREPARATION OF 3-CYANO-1-NAPHTHOIC ACID AND SOME ANALOGUES THEREOF

The present invention is related to a process for the preparation of 3-cyano-1-naphthoic acid and some analogues thereof of formula (1), the intermediate 1-halo-3-cyano naphthalene and some analogues thereof used in this process and a process for the preparation of said intermediate.

A new route for manufacture of 3-cyano-1-naphthalenecarboxylic acid

3-Cyano-1-naphthalenecarboxylic acid is an intermediate required for manufacture of tachykinin receptor antagonists. The 1,3-disubstitution pattern on the naphthalene skeleton complicates the synthesis of this cyano acid. Previous literature-based chemistry is unattractive for large-scale manufacture due to stoichiometric use of mercury salts, low yield, and other operational difficulties. An attractive new route has been developed by establishing the 1,3-substitution on the carbon atoms destined for only one-half of the naphthalene 2-ring system, via 3-bromocoumalate, and then building up the rest of the naphthalene ring system by Diels-Alder addition of 3-bromocoumalate to in situ-generated benzyne. The resulting 4-bromo-2-naphthoate was converted to the required cyanoacid by transformation of ester to nitrile followed by carbonylation of the bromo substituent. The new route has been scaled up successfully and offers significant advantages over previous literature chemistry in terms of improved process environmental implications, improved yield, lower cost, and improved robustness and ease of operation at larger scales of operation.

THERMAL CONVERSION OF METHYL 8-VINYL-3-OXO-2-OXABICYCLOOCT-5-EN-6-CARBOXYLATES TO TETRAHYDROCOUMARINS AND METHYL BENZOATES

Methyl 8-methyl- and 8-methoxy-8-vinyl-3-oxo-2-oxabicyclooct-5-en-6-carboxylates (3 and 5), prepared by the Diels-Alder reaction of methyl 2-oxo-2H-pyran-5-carboxylate with 2-methyl- and 2-methoxy-1,3-butadienes, were converted into methyl 9-methyl- and 9-methoxy-3-oxo-2-oxabicyclodeca-4,8-diene-6-carboxylates (tetrahydrocoumarins) by a Cope rearrangement at about 140 deg C, respectively.On the other hand, 3 and 5 were transformed into methyl 4-isopropyl- and 4-acetylbenzoates via the reaction of methyl tricyclo2,7>oct-3-en-4-carboxylates at about 257 deg C in the presence of Pd-C, respectively.