2459-05-4

Basic information

• Product Name: Monoethyl fumarate
• Synonyms: (2E)-4-Ethoxy-4-oxo-2-butenoic acid;2-Butenedioic acid (E)-, monoethyl ester;ETHYL ACID FUMARATE;ETHYL HYDROGEN FUMARATE;ETHYL FUMARATE;ETHYL FUMARATE MONOESTER;FUMARIC ACID MONOETHYL ESTER;AKOS BBB/201
• CAS NO: 2459-05-4
• Molecular Formula: C₆H₈O₄
• Molecular Weight: 144.13
• EINECS: 219-544-7
• Product Categories: Building Blocks;C6 to C7;Carbonyl Compounds;Chemical Synthesis;Esters;Organic Building Blocks;mildew preventive
• Mol File: 2459-05-4.mol
• Article Data: 29

Chemical Properties

• Melting Point: 66-68 °C(lit.)
• Boiling Point: 147 °C16 mm Hg(lit.)
• Flash Point: 109.6 °C
• Appearance: Almost white to beige/Crystalline Powder
• Density: 1.1109
• Vapor Pressure: 0.0034mmHg at 25°C
• Refractive Index: 1.4500 (estimate)
• Storage Temp.: Refrigerator
• Solubility: Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly)
• PKA: 3.45±0.10(Predicted)
• Water Solubility: Soluble in water.
• BRN: 1723588
• CAS DataBase Reference: Monoethyl fumarate(CAS DataBase Reference)
• NIST Chemistry Reference: Monoethyl fumarate(2459-05-4)
• EPA Substance Registry System: Monoethyl fumarate(2459-05-4)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 1
• HazardClass: IRRITANT
• Hazardous Substances Data: 2459-05-4(Hazardous Substances Data)

Usage

Description

Monoethyl fumarate is the Monoethyl ester form of fumarate. It is a kind of effective preservative and polymerization agent for macromolecular material. Monoethyl fumarate is capable of inhibiting the growth of bacteria, yeast and mold and prolonging the storage time of feed can. It can also be used for long-term systemic therapy in the treatment of psoriasis (a chronic hyperproliferative inflammatory skin disorder). It is the most active ingredient in the antipsoriasis drug Fumadem. The mechanism is likely to be related to its effect of improvement of keratinocyte differentiation and inhibition of keratinocyte proliferation. Monomethyl fumarate has beneficial effects on the inflamed blood–brain barrier. It increases levels of endogenous antioxidant proteins in brain endothelial cells and reduces expression of VCAM-1 in inflamed brain endothelial cells. Transendothelial monocyte migration is limited upon MMF treatment.

References

Thio, H. B., et al. "Long‐term systemic therapy with dimethylfumarate and monoethylfumarate (Fumaderm?;) in psoriasis." Journal of the European Academy of Dermatology & Venereology 4.1(1995):35-40. Asadullah, K, et al. "Influence of monomethylfumarate on monocytic cytokine formation--explanation for adverse and therapeutic effects in psoriasis?." Archives of Dermatological Research 289.11(1997):623-30. Lim, J. L., et al. "Protective effects of monomethyl fumarate at the inflamed blood-brain barrier." Microvascular Research 105(2016):61. Zhao, Wen Xiu, C. M. Zhang, and X. U. Xue-Ming. "Synthesis and antimicrobial active of monomethyl fumarate." Science & Technology of Food Industry (2008). Helwa, Inas. "The Mechanism of Monomethylfumarate (MMF) as an Anti-psoriatic Agent." Helwa Inas (2014)

Chemical Properties

ALMOST WHITE TO BEIGE CRYSTALLINE POWDER

Uses

Monoethyl fumarate is the monoethyl ester form of fumaric acid. Monoethyl fumarate is a kind of effective preservative and polymerization agent for macromolecular material.Monoethyl fumarate (fumaric acid monoethyl ester, monoethyl fumarate) was used in the preparation of photo-crosslinkable macromers. It was also used to synthesize Ugi/intramolecular Diels-Alder (IMDA) cycloaddition products.

Definition

ChEBI: Monomethyl fumarate is a dicarboxylic acid monoester resulting from the formal condensation of one of the carboxy groups of fumaric acid with methanol. Is is a metabolite of dimethyl fumarate and used for the the treatment of patients with relapsing multiple sclerosis (MS). It also induces the NFE2L2 (Nrf2) transcription factor by binding to KEAP1. It has a role as an immunomodulator, an antioxidant and a drug metabolite. It is an enoate ester, a methyl ester and a dicarboxylic acid monoester. It derives from a fumaric acid.

Preparation

Monomethyl fumarate was synthesized by maleic anhydride and methanol. It is used to treat relapsing forms of multiple sclerosis in adults (including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease).

InChI:InChI=1/C6H8O4/c1-2-10-6(9)4-3-5(7)8/h3-4H,2H2,1H3,(H,7,8)/p-1

Synthetic route

diethyl Fumarate (623-91-6) → (E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4)

Conditions	Yield
With potassium hydroxide In ethanol for 8h; Ambient temperature;	89%
With Candida antarctica lipase; water In 1,4-dioxane for 144h;	78%

ethyl acetate (141-78-6) + maleic acid (110-16-7) → (E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4)

Conditions	Yield
With iron(III) perchlorate for 2h; Ambient temperature;	87%

carbon dioxide (124-38-9) + 3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-acrylic acid ethyl ester (1263187-14-9) → (E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4)

Conditions	Yield
With potassium methanolate; copper(l) chloride In N,N-dimethyl acetamide at 70℃; under 760.051 Torr; for 24h; Inert atmosphere; Schlenk technique; Sealed tube;	76%

ethyl (2E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate (1009307-13-4) + carbon dioxide (124-38-9) → (E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4)

Conditions	Yield
With potassium methanolate; copper(l) chloride In N,N-dimethyl acetamide at 70℃; for 24h; Sealed tube; Schlenk technique;	76%

malonic acid monoethyl ester (2459-05-4, 3249-53-4, 3990-03-2) → (E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4)

Conditions	Yield
With aluminum (III) chloride at 70℃; for 2h;	58%

diazoacetic acid ethyl ester (623-73-4) + ethyl 2-diazo-3-methyl-3-butenoate (126580-11-8) → malonic acid monoethyl ester (2459-05-4, 3249-53-4, 3990-03-2) + (E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) + diethyl 2-methylcyclobutene-1,3-dicarboxylate (1198173-63-5)

Conditions	Yield
With tetrakis(acetonitrile)copper(I)tetrafluoroborate In dichloromethane at 20℃; for 2h; Inert atmosphere;	A n/a B n/a C 33%

maleic anhydride (108-31-6) + ethanol (64-17-5) → (E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4)

Conditions	Yield
With thionyl chloride
With TEA
Stage #1: maleic anhydride; ethanol at 60℃; for 3h; Stage #2: With aluminum (III) chloride at 20 - 90℃; for 2h;

ethanol (64-17-5) + malic acid (617-48-1) → (E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) + diethyl Fumarate (623-91-6)

Conditions	Yield
With hydrogenchloride

ethanol (64-17-5) + (2E)-but-2-enedioic acid (110-17-8) → (E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4)

Conditions	Yield
at 120℃;
With hydrogenchloride

ethanol (64-17-5) + (2E)-but-2-enedioic acid (110-17-8) → (E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) + diethyl Fumarate (623-91-6)

Conditions	Yield
With sulfuric acid
at 120℃;

Diethyl maleate (141-05-9) → (E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4)

Conditions	Yield
With potassium hydroxide; ethanol Schuetteln, Filtrieren, Verdunsten des Filtrats, Loesen des Rueckstands in Wasser und Schuetteln mit Aether aus; der waessr.Loesung mit Salzsaeure Uebersaettigen und mit Aether Ausschuetteln;

1,3,5,7,9,10-hexahydro-3,7,10-trimethylpyrimido<5,4-g>pteridine-2,4,6,8-tetrone (82639-48-3) + diethyl Fumarate (623-91-6) → (E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) + 3,7,10-trimethyl-(1H,3H,7H,10H)-pyrimido<5-4-g>pteridine-2,4,6,8-tetrone (82639-46-1) + (2E)-but-2-enedioic acid (110-17-8) + succinic acid diethyl ester (123-25-1)

Conditions	Yield
In N,N-dimethyl-formamide at 30℃; for 12h; Rate constant; pH=7.00;	A 19 % Spectr. B n/a C 10 % Spectr. D 32 % Chromat.

selenium(IV) oxide (7446-08-4) + succinic acid diethyl ester (123-25-1) → (E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) + diethyl Fumarate (623-91-6)

Conditions	Yield
at 170℃;

glyoxylic acid ethyl ester (924-44-7) + diethylphosphonoacetic acid (3095-95-2) → (E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4)

Conditions	Yield
Stage #1: diethylphosphonoacetic acid With sodium hydride In 1,2-dimethoxyethane at 20℃; Stage #2: glyoxylic acid ethyl ester In 1,2-dimethoxyethane at 20℃; Further stages.;

maleic anhydride (108-31-6) → (E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4)

Conditions	Yield
iodine In ethanol

but-2-enedioic acid tert-butyl ester ethyl ester (107679-25-4) → (E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4)

Conditions	Yield
With water Alkaline conditions;

malonic acid monoethyl ester (2459-05-4, 3249-53-4, 3990-03-2) + thiourea (17356-08-0) → (E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4)

Conditions	Yield
In water at 80 - 85℃; for 4h;	112 g

[(dimethoxyphosphinothioyl)thio]-butanedioic acid, diethyl ester (121-75-5) → malathion alpha-dicarboxylic acid (1190-28-9) + (E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) + S-(1,2-dicarboethoxyethyl)O,S-dimethyl phosphorodithioate (3344-12-5) + malathion monocarboxylic acid (1190-29-0) + oxallic acid isobutyle nonyl ester + Diethyl maleate (141-05-9)

Conditions	Yield
With carboxylesterase from Escherichia coli IES-02 In aq. phosphate buffer at 37℃; for 1h; pH=7.5; Catalytic behavior; Enzymatic reaction;

Sorbyl alcohol (17102-64-6) + (E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) → ethyl (2E,4E)-hexa-2,4-dien-1-yl fumarate (160386-62-9)

Conditions	Yield
With dmap; 2`,3`-dideoxycytidine In dichloromethane Ambient temperature;	100%
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃; for 3.5h;	90%

(E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) + octa-4t,6t-dien-3-ol (186417-99-2) → (E)-But-2-enedioic acid ethyl ester (2E,4E)-1-ethyl-hexa-2,4-dienyl ester (186418-00-8)

Conditions	Yield
With dmap; 2`,3`-dideoxycytidine In dichloromethane Ambient temperature;	100%

(E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) + 4-methoxy-aniline (104-94-9) → (E)–4-((4-methoxyphenyl)amino)-4-oxobut-2-enoic acid (37904-20-4)

Conditions	Yield
Stage #1: (E)-4-ethoxy-4-oxobut-2-enoic acid With oxalyl dichloride; N,N-dimethyl-formamide In benzene at 20℃; for 4h; Inert atmosphere; Stage #2: 4-methoxy-aniline With caesium carbonate In tetrahydrofuran at 20℃; Inert atmosphere; Stage #3: With potassium hydroxide; water In tetrahydrofuran at 20℃; for 4h; Inert atmosphere;	100%

(E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) + 4-nitro-aniline (100-01-6) → fumaric acid mono-N-(4-nitrophenyl)amide (37904-21-5)

Conditions	Yield
Stage #1: (E)-4-ethoxy-4-oxobut-2-enoic acid With oxalyl dichloride; N,N-dimethyl-formamide In benzene at 20℃; for 4h; Inert atmosphere; Stage #2: 4-nitro-aniline With caesium carbonate In tetrahydrofuran at 20℃; Inert atmosphere; Stage #3: With potassium hydroxide; water In tetrahydrofuran at 20℃; for 4h; Inert atmosphere;	100%

(E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) + (-)-(4E,6Z)-(1'R,2R,3S)-1,2,3-trihydroxy-1,3-O-ethylidene-4,6-octadiene (937172-42-4) → (-)-(4E,6Z)-(1'R,2R,3S)-1,3-dihydroxy-1,3-O-ethylidene-4,6-octadien-2-yl ethyl fumarate (937172-48-0)

Conditions	Yield
Stage #1: (E)-4-ethoxy-4-oxobut-2-enoic acid With dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 0.166667h; Inert atmosphere; Stage #2: With dmap In dichloromethane at 20℃; for 0.166667h; Inert atmosphere; Stage #3: (-)-(4E,6Z)-(1'R,2R,3S)-1,2,3-trihydroxy-1,3-O-ethylidene-4,6-octadiene In dichloromethane for 1h; Inert atmosphere; Reflux;	100%

(E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) + tert-butylisonitrile (119072-55-8, 7188-38-7) + 4-hydroxy-1-naphthaldehyde (7770-45-8) + 4-aminomethylphenol (696-60-6) → C29H32N2O6

Conditions	Yield
With lithium chloride; sodium hydroxide In water at 50℃; under 7500.75 Torr; for 1h; pH=7; Inert atmosphere; Microwave irradiation;	100%

(E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) + tert-butylisonitrile (119072-55-8, 7188-38-7) + 4-hydroxy-1-naphthaldehyde (7770-45-8) + benzylamine (100-46-9) → C29H32N2O5

Conditions	Yield
With lithium chloride; sodium hydroxide In water at 50℃; under 7500.75 Torr; for 1h; pH=7; Inert atmosphere; Microwave irradiation;	100%

(E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) + N-methyl-1-naphthalenemethylamine hydrochloride (65473-13-4) → trans-3-(N-methyl-1-naphthylmethylcarbamoyl)propenoic acid ethyl ester

Conditions	Yield
Stage #1: (E)-4-ethoxy-4-oxobut-2-enoic acid With 4-methyl-morpholine; isobutyl chloroformate In dichloromethane Stage #2: N-methyl-1-naphthalenemethylamine hydrochloride In dichloromethane Further stages.;	99%
Stage #1: (E)-4-ethoxy-4-oxobut-2-enoic acid With 4-methyl-morpholine; isobutyl chloroformate In dichloromethane at -20℃; for 0.5h; Stage #2: N-methyl-1-naphthalenemethylamine hydrochloride In dichloromethane at 20℃; for 4h; Further stages.;	99%

piperidine (110-89-4) + (E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) → trans-3-(1-piperidylcarbonyl)propenoic acid ethyl ester (92912-62-4)

Conditions	Yield
Stage #1: (E)-4-ethoxy-4-oxobut-2-enoic acid With 4-methyl-morpholine; isobutyl chloroformate In dichloromethane at -20℃; for 0.5h; Stage #2: piperidine In dichloromethane at 20℃; for 4h; Further stages.;	99%

(E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) + N-methylaniline (100-61-8) → (E)-4-(methylphenylamino)-4-oxo-2-butenoic acid ethyl ester (1027101-46-7)

Conditions	Yield
Stage #1: (E)-4-ethoxy-4-oxobut-2-enoic acid With 4-methyl-morpholine; isobutyl chloroformate In dichloromethane at -20℃; for 0.5h; Stage #2: N-methylaniline In dichloromethane at 20℃; for 4h; Further stages.;	99%

(E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) + benzyl-methyl-amine (103-67-3) → (E)-4-[methyl(phenylmethyl)amino]-4-oxo-2-butenoic acid ethyl ester (945379-56-6)

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 25℃;	98%
	76%
Stage #1: (E)-4-ethoxy-4-oxobut-2-enoic acid With 4-methyl-morpholine; isobutyl chloroformate In dichloromethane Stage #2: benzyl-methyl-amine In dichloromethane Further stages.;	76%
Stage #1: (E)-4-ethoxy-4-oxobut-2-enoic acid With 4-methyl-morpholine; isobutyl chloroformate In dichloromethane at -20℃; for 0.5h; Stage #2: benzyl-methyl-amine In dichloromethane at 20℃; for 4h; Further stages.;	76%

(E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) → fumaric acid ethyl ester mono chloride (26367-48-6)

Conditions	Yield
With thionyl chloride at 20℃; for 24h;	97%
With oxalyl dichloride In N,N-dimethyl-formamide	93%
With dmap; oxalyl dichloride In dichloromethane at 20℃; for 1.5h;	93%

(E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) + (+/-)-2-(Bromomethyl)-1-butanol (40893-97-8) → (+/-)-Ethyl (E)-3-((2-(bromomethyl)butoxy)carbonyl)prop-2-enoate (155529-26-3)

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide	97%
With dmap; dicyclohexyl-carbodiimide In dichloromethane for 2h; Ambient temperature;	97%

(E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) + Di(tert-butyl)-N-(3-aminopropyl)-N,N'-(ethan-1,2-diyl)bis (142039-01-8) → 3-{3-[BOC-(2-BOC-Aminoethyl)-amino]-propylcarbamoyl}-acrylic acid ethyl ester

Conditions	Yield
With dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 3h;	97%

(E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) + (2E)-3-(1-dimethylsulfamoyl-1H-imidazol-4-yl)prop-2-en-1-ol (610768-33-7) → (2E)-2-butenedioic acid (2E)-3-(1-dimethylsulfamoyl-1H-imidazol-4-yl)-2-propenyl ester ethyl ester (610768-45-1)

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane at -78 - 20℃; for 4h;	97%

(E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) + Benzyl isocyanide (88333-03-3, 10340-91-7) + pivalaldehyde (630-19-3) + benzylamine (100-46-9) → (E)-ethyl 4-(benzyl(1-(benzylamino)-3,3-dimethyl-1-oxobutan-2-yl)amino)-4-oxobut-2-enoate

Conditions	Yield
In dichloromethane at 200℃; under 13501.4 Torr; for 0.333333h; Ugi reaction; microwave irradiation;	97%

(E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) + C8H13N3O3S (220378-49-4) → (2E)-2-butenedioic acid (2E)-3-(1-dimethylsulfamoyl-1H-imidazol-4-yl)-2-propenyl ester ethyl ester (610768-45-1)

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 20℃; Inert atmosphere;	97%

N-(2-pyrimidyl)indole (221044-05-9) + (E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) → (E)-3-(1-pyrimidin-2-yl-1H-indol-2-yl)-acrylic acid ethyl ester

Conditions	Yield
With bis(1,5-cyclooctadiene)rhodium(I) trifluoromethanesulfonate; 2,2-dimethylpropanoic anhydride In toluene at 140℃; for 1h; Inert atmosphere; stereoselective reaction;	97%

(E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) + benzyl bromide (100-39-0) → 1-benzyl-4-ethyl-(2E)-but-2-endioate

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 12h;	97%
With potassium carbonate In N,N-dimethyl-formamide at 55℃; for 16h;	42.9 g

(E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) + (-)-(E)-(1'R,2R,3S)-1,2,3-trihydroxy-1,3-O-ethylidene-5-methyl-4,6-heptadiene (1310682-99-5) → (-)-(E)-(1'R,2R,3S)-1,3-dihydroxy-1,3-O-ethylidene-5-methyl-4,6-heptadien-2-yl ethyl fumarate (1310683-04-5)

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane for 1h; Inert atmosphere; Reflux;	96%

(E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) + pivaloyl chloride (3282-30-2) → C11H16O5

Conditions	Yield
With triethylamine In dichloromethane at -25 - 20℃; Solvent; Temperature; Time; Cooling with acetone-dry ice;	96%

(E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) + Benzyl isocyanide (88333-03-3, 10340-91-7) + β-naphthaldehyde (66-99-9) + 4-methoxy-benzylamine (2393-23-9) → (E)-ethyl 4-((2-(benzylamino)-1-(naphthalen-2-yl)-2-oxoethyl)(4-methoxybenzyl)amino)-4-oxobut-2-enoate

Conditions	Yield
In dichloromethane at 200℃; under 13501.4 Torr; for 0.333333h; Ugi reaction; microwave irradiation;	95%

(E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) + tert-butylisonitrile (119072-55-8, 7188-38-7) + α-methyl-p-hydroxybenzylamine (134855-87-1) + pivalaldehyde (630-19-3) → C24H36N2O5

Conditions	Yield
In water at 200℃; under 13501.4 Torr; microwave irradiation;	95%

(E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) + N-benzyl-1-(4-fluorophenyl)methanamine (55096-88-3) → trans-3-(benzyl-4-fluorobenzyl)carbamoylpropenoic acid ethyl ester (1027101-48-9)

Conditions	Yield
Stage #1: (E)-4-ethoxy-4-oxobut-2-enoic acid With 4-methyl-morpholine; isobutyl chloroformate In dichloromethane at -20℃; for 0.5h; Stage #2: N-benzyl-1-(4-fluorophenyl)methanamine In dichloromethane at 20℃; for 4h; Further stages.;	95%

(E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) + dibutylamine (111-92-2) → trans-3-dibutylcarbamoylpropenoic acid ethyl ester (109447-28-1)

Conditions	Yield
Stage #1: (E)-4-ethoxy-4-oxobut-2-enoic acid With 4-methyl-morpholine; isobutyl chloroformate In dichloromethane at -20℃; for 0.5h; Stage #2: dibutylamine In dichloromethane at 20℃; for 4h; Further stages.;	95%

(E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) + diethylamine (109-89-7) → trans-3-diethylcarbamoylpropenoic acid ethyl ester (110793-11-8)

Conditions	Yield
Stage #1: (E)-4-ethoxy-4-oxobut-2-enoic acid With 4-methyl-morpholine; isobutyl chloroformate In dichloromethane at -20℃; for 0.5h; Stage #2: diethylamine In dichloromethane at 20℃; for 4h; Further stages.;	95%

morpholine (110-91-8) + (E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) → (E)-4-(4-morpholinyl)-4-oxo-2-butenoic acid ethyl ester (92912-63-5)

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 25℃;	95%

(S)-3-amino-2-(tert-butyldiphenylsilanyloxy)propylcarbamic acid tert-butyl ester (1007217-08-4) + (E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) → C30H42N2O6Si (1373889-07-6)

Conditions	Yield
With benzotriazol-1-ol; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 0 - 20℃; for 12h; Inert atmosphere;	94%

isocyanate de chlorosulfonyle (1189-71-5) + (E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) → (E)-4-ethoxy-4-oxobut-2-enoic anhydride (675876-18-3)

Conditions	Yield
With triethylamine In dichloromethane at -25 - 10℃; for 6.5h; Solvent; Temperature; Time; Cooling with acetone-dry ice;	94%

(E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) + 2,2-Diphenylethylamine (3963-62-0) → fumaric acid mono-2,2-diphenylethylamide monoethyl ester (573986-11-5)

Conditions	Yield
With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In dichloromethane at 20℃; for 20h;	93%
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane	85%
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane for 24h;	85%
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 20℃; for 48h; Inert atmosphere;	71%

Upstream product

• 108-31-6 maleic anhydride 
• 64-17-5 ethanol 
• 110-17-8 (2E)-but-2-enedioic acid 
• 623-91-6 diethyl Fumarate 
• 2459-05-4 malonic acid monoethyl ester 
• 17356-08-0 thiourea 
• 1009307-13-4 ethyl (2E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate 
• 124-38-9 carbon dioxide 
• 1263187-14-9 3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-acrylic acid ethyl ester 
• 121-75-5 [(dimethoxyphosphinothioyl)thio]-butanedioic acid, diethyl ester 
• 107679-25-4 but-2-enedioic acid tert-butyl ester ethyl ester 
• 623-73-4 diazoacetic acid ethyl ester 
• 126580-11-8 ethyl 2-diazo-3-methyl-3-butenoate 
• 924-44-7 glyoxylic acid ethyl ester 

Downstream Products

• 108-31-6 maleic anhydride 
• 107594-90-1 (E)-But-2-enedioic acid cyclohexyl ester ethyl ester 
• 160386-62-9 ethyl (2E,4E)-hexa-2,4-dien-1-yl fumarate 
• 221482-76-4 2-(2'-ethoxycarbonyl)acryloyl-3-phenyl-l-menthopyrazole 
• 300655-00-9 (E)-But-2-enedioic acid ethyl ester 2-[(1S,4R)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]hept-(2E)-ylidenemethyl]-phenyl ester 
• 685543-66-2 AEPI-2 
• 685543-87-7 3-{N-(3-tert-butoxycarbonylamino-propyl)-N'-[4-methyl-2-(3-phenyl-propionylamino)-pentanoyl]-hydrazinocarbonyl}-acrylic acid ethyl ester 
• 685543-88-8 3-{N-(4-tert-butoxycarbonylamino-butyl)-N'-[4-methyl-2-(3-phenyl-propionylamino)-pentanoyl]-hydrazinocarbonyl}-acrylic acid ethyl ester 
• 685543-84-4 3-(N'-{2-[2-(2-benzyloxycarbonylamino-4-methyl-pentanoylamino)-4-tert-butoxycarbonyl-butyrylamino]-3-hydroxy-butyryl}-N-tert-butoxycarbonylmethyl-hydrazinocarbonyl)-acrylic acid ethyl ester 
• 685543-79-7 3-(N'-{2-[2-(2-benzyloxycarbonylamino-3-tert-butoxycarbonyl-propionylamino)-4-tert-butoxycarbonyl-butyrylamino]-3-methyl-butyryl}-N-tert-butoxycarbonylmethyl-hydrazinocarbonyl)-acrylic acid ethyl ester 

Relevant articles and documents

Action of alpha-chymotrypsin on the diethyl esters of fumaric, maleic, and acetylenedicarboxylic acids.

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Kras-G12C inhibitor heterocyclic compounds

The invention relates to Kras-G12C inhibitor heterocyclic compounds represented by formula I, a preparation method thereof, and application of the Kras-G12C inhibitor heterocyclic compounds in prevention and treatment of tumor diseases such as lung cancer, colorectal cancer and pancreatic cancer. In the preparation process, the compounds of the general formula I are obtained through a series of reactions such as SN2 reaction, protection, coupling reaction, deprotection, condensation reaction and the like.

Method for preparing alpha, beta-unsaturated carboxylic acid by reacting alkenyl boron compound with carbon dioxide under catalysis of cuprous halide

The invention discloses a method for preparing alpha, beta-unsaturated carboxylic acid through a carboxylation reaction of an alkenyl boron compound and carbon dioxide under the catalysis of cuprous halide. According to the method, carbon dioxide is used as a C1 source, the cuprous halide is adopted for catalysis, and alkoxide serves as alkali to react in an organic solvent, so the method is simple and easy to implement, has a wide substrate application range, converts various alkenyl boron compounds such as alkenyl boric acid, alkenyl borate and borate into corresponding alpha, beta-unsaturated carboxylic acid under mild conditions, and has a very high yield. The obtained product alpha, beta-unsaturated carboxylic acid is an important intermediate for preparing fine chemical products suchas perfumes, insecticides and the like.

A comparative study on degradation of complex malathion organophosphate using of Escherichia coli IES-02 and a novel carboxylesterase

Malathion organophosphates considered as the major constituent of herbicides, pesticides and insecticides. Extensively used in agricultural, horticultures and for numerous household applications contributes to precedence organic pollutants leading antagonistic effects on human health and environment. Therefore detoxification of malathion from contaminated site is of general interest. Simultaneously it is very emerging to isolated novel indigenous microbial strains from contaminated site with a record of pesticide application. In this study Escherichia coli IES-02 isolated from malathion contaminant effluent and the strain showed maximum efficiency in malathion degradation that utilized it as the sole source of carbon. Carboxylesterase (33.0, 30.0, 28.0 kDa) were purified (1685.71 U/mg) from Escherichia coli IES-02 showed significant results in malathion degradation approximately 81% within 20 min as compared with Escherichia coli IES-02 cells within 4 h (99.0 to 95.0%) into monocarboxylic acid and diacid derivatives. The generation time of Escherichia coli was also observed at 60 min with 0.1 ppm, 68 min with 0.5 ppm, 74.5 min with 2.0 ppm and 91.37 min with 50 ppm of malathion. The degradation rate and transformation metabolites were estimated by Gas Chromatography-Mass Spectrometry respectively. Malathion metabolites pathway proposed in this study which revealed the potential application against lethal environmental pollution.