453-18-9

Basic information

• Product Name: Methyl fluoroacetate
• Synonyms: Acetic acid, fluoro-, methyl ester;Aceticacid,fluoro-,methylester;Fluoracetic acid methyl ester;fluoro-aceticacimethylester;Methylester kyseliny fluoroctove;methylesterkyselinyfluoroctove;TL 551;tl551
• CAS NO: 453-18-9
• Molecular Formula: C₃H₅FO₂
• Molecular Weight: 92.07
• EINECS: 207-218-7
• Product Categories: Fluoro-Aliphatics
• Mol File: 453-18-9.mol
• Article Data: 4

Chemical Properties

• Melting Point: -40 °C
• Boiling Point: 104 °C
• Flash Point: 17.6 °C
• Appearance: Colorless, transparent liquid
• Density: 1.17
• Vapor Pressure: 0.000941mmHg at 25°C
• Refractive Index: 1.3650 to 1.3680
• Merck: 14,4167
• CAS DataBase Reference: Methyl fluoroacetate(CAS DataBase Reference)
• NIST Chemistry Reference: Methyl fluoroacetate(453-18-9)
• EPA Substance Registry System: Methyl fluoroacetate(453-18-9)

Safety Data

• Hazard Codes: T
• Statements: 10-36/37/38
• Safety Statements: 16-26-36
• RIDADR: 3272
• RTECS: AH8400000
• HazardClass: TOXIC
• PackingGroup: I
• Hazardous Substances Data: 453-18-9(Hazardous Substances Data)

Usage

Description

Methyl fluoroacetate, also known as fluoroacetate or compound 1080, is a colorless and transparent liquid with a slightly sweet taste. It is a highly toxic compound that can be used in various applications due to its unique chemical properties.

Uses

Used in Pharmaceutical Industry:
Methyl fluoroacetate is used as an intermediate for the synthesis of various pharmaceutical compounds. Its unique chemical structure allows it to be a key component in the development of new drugs with potential therapeutic applications.
Used in Pesticide Industry:
In the pesticide industry, methyl fluoroacetate is used as a highly effective and lethal compound for controlling pests, particularly rodents. Its high toxicity makes it a potent tool in pest management, although its use is strictly regulated due to its potential hazards to non-target species and the environment.
Used in Dye Industry:
Methyl fluoroacetate is also utilized as an intermediate in the production of certain dyes and pigments. Its chemical properties enable the creation of vibrant and stable colorants for various applications, including textiles, plastics, and printing inks.

InChI:InChI=1/C8H4BrF3O3/c9-5-1-4(7(13)14)2-6(3-5)15-8(10,11)12/h1-3H,(H,13,14)

Synthetic route

3-ethoxyprop-1-ene (557-31-3) + Methyl fluoroiodoacetate (181224-33-9) → methyl fluoroacetate (453-18-9) + 5-Ethoxy-2-fluoro-4-iodo-pentanoic acid methyl ester

Conditions	Yield
With iron In tetrahydrofuran for 12h; Heating;	A 9 % Spectr. B 82%

Methyl fluoroiodoacetate (181224-33-9) → methyl fluoroacetate (453-18-9) + Propionic acid 1-fluoro-2-(4-iodomethyl-tetrahydro-furan-3-yl)-ethyl ester

Conditions	Yield
With Allyl ether; iron In tetrahydrofuran for 13h; Heating;	A 11 % Spectr. B 81%

methyl chloroacetate (96-34-4) → methyl fluoroacetate (453-18-9)

Conditions	Yield
With potassium fluoride; tetrabutylammomium bromide for 1.25h; Heating;	79%
With acetamide; potassium fluoride at 100 - 110℃; for 3h; Substitution;	30%
With acetamide; potassium fluoride at 100 - 110℃; for 3h; Substitution;	30%

acrylonitrile (107-13-1) + Methyl fluoroiodoacetate (181224-33-9) → methyl fluoroacetate (453-18-9) + 4-Cyano-2-fluoro-butyric acid methyl ester

Conditions	Yield
With [2,2]bipyridinyl; chromium chloride; iron In methanol at 70 - 80℃; for 10h;	A 14 % Spectr. B 74%

acrylic acid methyl ester (292638-85-8) + Methyl fluoroiodoacetate (181224-33-9) → methyl fluoroacetate (453-18-9) + Dimethyl 2-fluoropentanedioate (7766-74-7)

Conditions	Yield
With [2,2]bipyridinyl; chromium chloride; iron In methanol at 70 - 80℃; for 11h;	A 17 % Spectr. B 71%

methanol (67-56-1) + fluoroacetamide (640-19-7) → methyl fluoroacetate (453-18-9)

Conditions	Yield
With boron trifluoride

methyl 2-iodoacetate (5199-50-8) → methyl fluoroacetate (453-18-9)

Conditions	Yield
With silver fluoride at 170℃;
With mercury(II) fluoride at 170℃;

bromoacetic acid methyl ester (96-32-2) → methyl fluoroacetate (453-18-9)

Conditions	Yield
With thallium(I) fluoride; ethanol
With potassium fluoride; acetylacetone Irradiation.UV-Licht;

methanol (67-56-1) + perfluoropropylene (116-15-4) → methyl fluoroacetate (453-18-9)

Conditions	Yield
With carbon dioxide; sodium In acetone

methanol (67-56-1) + monofluoroacetyl chloride (359-06-8) → methyl fluoroacetate (453-18-9)

ethanol (64-17-5) + bromoacetic acid methyl ester (96-32-2) + Tlf → methyl fluoroacetate (453-18-9)

dimethyl sulfate (77-78-1) + sodium-fluoroacetate → methyl fluoroacetate (453-18-9)

methyl fluoroacetate (453-18-9) + allyl S-(5-amido-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonicacid)-(2→6)-2-acetamido-2-deoxy-6-thio-α-Dgalactopyranoside → allyl S-(5-fluoroacetamido-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonic acid)-(2→6)-2-acetamido-2-deoxy-6-thio-α-D-galactopyranoside

Conditions	Yield
With triethylamine In methanol Inert atmosphere; Reflux;	100%

methyl fluoroacetate (453-18-9) → sodium fluoroacetate (62-74-8)

Conditions	Yield
With sodium hydroxide In tetrahydrofuran for 2h; Reflux;	94%

(R)-N-benzylidene-2-methylpropane-2-sulfinamide (196929-85-8) + methyl fluoroacetate (453-18-9) → (RS,2R,3S)-2-fluoro-3-(2-methylpropane-2-sulfinylamino)-3-phenylpropionic acid methyl ester

Conditions	Yield
With lithium hexamethyldisilazane In tetrahydrofuran at -80℃; for 0.5h; Inert atmosphere;	88%
With N,N,N,N,-tetramethylethylenediamine; lithium hexamethyldisilazane In tetrahydrofuran at -70℃; for 0.5h; Inert atmosphere; diastereoselective reaction;	85%

tris(methylthio)methane (5418-86-0) + methyl fluoroacetate (453-18-9) → 3-Fluoro-1,1,1-tris-methylsulfanyl-propan-2-one

Conditions	Yield
With n-butyllithium In tetrahydrofuran; hexane 1.) -95 deg C, 2 h, 2.) -95 deg C, 5 min;	87%

methyl fluoroacetate (453-18-9) + allyl 4-O-(5-amino-3,5-dideoxy-α-D-neuraminopyranosyl)-2-acetylamino-2-deoxy-α-D-galactopyranoside → C22H35FN2O14 (1263480-77-8)

Conditions	Yield
With triethylamine In methanol at 20℃; Inert atmosphere; Cooling with ice;	85%
With triethylamine In methanol at 20℃; Inert atmosphere; Cooling with ice;

methyl fluoroacetate (453-18-9) + (R)-(-)-N-(4-chlorobenzylidene)-2-methylpropane-2-sulfinamide (507469-89-8) → C14H19ClFNO3S + (RS,2R,3S)-3-(4-chlorophenyl)-2-fluoro-3-(2-methylpropane-2-sulfinylamino)propionic acid methyl ester

Conditions	Yield
With N,N,N,N,-tetramethylethylenediamine; lithium hexamethyldisilazane In tetrahydrofuran at -70℃; for 0.5h; Inert atmosphere; diastereoselective reaction;	A n/a B 83%
With potassium tert-butylate In tetrahydrofuran at 30℃; for 0.5h; Inert atmosphere; Overall yield = 83 %;	A n/a B n/a

1-methoxy-2-methyl-1-trimethylsiloxy-1-propene (31469-15-5) + trimethylsilyl cyanide (7677-24-9) + methyl fluoroacetate (453-18-9) → methyl 3-cyano-4-fluoro-2,2-dimethyl-3-trimethylsilyloxybutanoate

Conditions	Yield
With gallium(III) iodide In dichloromethane at 20℃; for 5h;	82%

methyl fluoroacetate (453-18-9) + C17H17Cl2NOS (1547490-94-7) → (RS,2R)-3,3-bis(4-chlorophenyl)-2-fluoro-3-(2-methylpropane-2-sulfinylamino)propionic acid methyl ester + C20H22Cl2FNO3S

Conditions	Yield
With N,N,N,N,-tetramethylethylenediamine; lithium hexamethyldisilazane In tetrahydrofuran at -70℃; for 0.5h; Inert atmosphere; diastereoselective reaction;	A 82% B n/a

methyl fluoroacetate (453-18-9) + (S)-5-(aminomethyl)-3-(3-fluoro-4-(4-(pyridin-2-yl)-1H-pyrazol-1-yl)phenyl)oxazolidin-2-one → (S)-2-fluoro-N-((3-(3-fluoro-4-(4-(pyridin-2-yl)-1H-pyrazol-1-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide

Conditions	Yield
In 2,2,2-trifluoroethanol at 80℃; for 15h;	81%

methyl fluoroacetate (453-18-9) + C12H17NOS (1015198-46-5) → C15H22FNO3S + (RS,2R,3S)-2-fluoro-3-(2-methylpropane-2-sulfinylamino)-3-p-tolylpropionic acid methyl ester

Conditions	Yield
With N,N,N,N,-tetramethylethylenediamine; lithium hexamethyldisilazane In tetrahydrofuran at -70℃; for 0.5h; Inert atmosphere; diastereoselective reaction;	A n/a B 80%
With sodium hexamethyldisilazane In tetrahydrofuran; dichloromethane at -20℃; for 0.5h; Inert atmosphere; Overall yield = 80 %; Overall yield = 252 mg;	A n/a B n/a

formaldehyd (50-00-0) + methyl fluoroacetate (453-18-9) → methyl 2-fluoroprop-2-enoate (2343-89-7)

Conditions	Yield
Stage #1: methyl fluoroacetate With Dimethyl oxalate; sodium methylate In dimethyl sulfoxide at 15 - 25℃; for 1h; Inert atmosphere; Stage #2: formaldehyd With 2,6-di-tert-butyl-4-methyl-phenol In dimethyl sulfoxide at 20 - 35℃; for 1h; Temperature; Reagent/catalyst; Inert atmosphere;	79.3%
Stage #1: methyl fluoroacetate With Dimethyl oxalate; sodium methylate In methanol; pentane at 20 - 25℃; for 24.25h; Claisen Condensation; Stage #2: formaldehyd In pentane at 5 - 10℃; for 5h; Concentration; Reagent/catalyst; Temperature; Time;	58%

methyl fluoroacetate (453-18-9) + (R)-2-methyl-N-(3-(trifluoromethyl)benzylidene)propane-2-sulfinamide → (RS,2R,3S)-2-fluoro-3-(2-methylpropane-2-sulfinylamino)-3-(3-trifluoromethylphenyl)propionic acid methyl ester + C15H19F4NO3S

Conditions	Yield
With N,N,N,N,-tetramethylethylenediamine; lithium hexamethyldisilazane In tetrahydrofuran at -70℃; for 0.5h; Inert atmosphere; diastereoselective reaction;	A 77% B n/a

methyl fluoroacetate (453-18-9) + 2-methylpropane-2-sulfinic acid [1-(2-methyl-1-ylphenyl)ethylidene]amide (1208989-34-7) → C15H22FNO3S + (RS,2R,3S)-2-fluoro-3-(2-methylpropane-2-sulfinylamino)-3-o-tolylpropionic acid methyl ester

Conditions	Yield
With N,N,N,N,-tetramethylethylenediamine; lithium hexamethyldisilazane In tetrahydrofuran at -70℃; for 0.5h; Inert atmosphere; diastereoselective reaction;	A n/a B 76%
With potassium hexamethylsilazane In tetrahydrofuran; N,N-dimethyl-formamide at -40℃; for 0.5h; Inert atmosphere; Overall yield = 88 %; Overall yield = 277 mg;	A n/a B n/a

methyl fluoroacetate (453-18-9) + (R)-N-(4-bromobenzylidene)-2-methylpropane-2-sulfinamide → (RS,2R,3S)-3-(4-bromophenyl)-2-fluoro-3-(2-methylpropane-2-sulfinylamino)propionic acid tert-butyl ester + C14H19BrFNO3S

Conditions	Yield
With N,N,N,N,-tetramethylethylenediamine; lithium hexamethyldisilazane In tetrahydrofuran at -70℃; for 0.5h; Inert atmosphere; diastereoselective reaction;	A 76% B n/a

methyl fluoroacetate (453-18-9) + C24H41NO18 → C26H42FNO19

Conditions	Yield
With triethylamine In methanol at 0 - 50℃; Inert atmosphere;	75%

methyl fluoroacetate (453-18-9) + C12H17NOS → C15H22FNO3S + (RS,2R,3S)-2-fluoro-3-(2-methylpropane-2-sulfinylamino)-3-m-tolylpropionic acid methyl ester

Conditions	Yield
With N,N,N,N,-tetramethylethylenediamine; lithium hexamethyldisilazane In tetrahydrofuran at -70℃; for 0.5h; Inert atmosphere; diastereoselective reaction;	A n/a B 74%
With sodium t-butanolate In tetrahydrofuran at 10℃; for 0.5h; Inert atmosphere; Overall yield = 74 %; Overall yield = 233 mg;	A n/a B n/a

methyl fluoroacetate (453-18-9) + (R)-(-)-N-(4-cyanobenzylidene)-2-methylpropane-2-sulfinamide (935263-24-4) → (RS,2R,3S)-3-(4-cyanophenyl)-2-fluoro-3-(2-methylpropane-2-sulfinylamino)propionic acid methyl ester + C15H19FN2O3S

Conditions	Yield
With N,N,N,N,-tetramethylethylenediamine; lithium hexamethyldisilazane In tetrahydrofuran at -70℃; for 0.5h; Inert atmosphere; diastereoselective reaction;	A 71% B n/a

N-tert-butylsulfinyl ketoimine (891782-22-2) + methyl fluoroacetate (453-18-9) → C20H24FNO3S + C20H24FNO3S

Conditions	Yield
With N,N,N,N,-tetramethylethylenediamine; lithium hexamethyldisilazane In tetrahydrofuran at -70℃; for 0.5h; Inert atmosphere; diastereoselective reaction;	A 71% B n/a

methyl fluoroacetate (453-18-9) + (RS)-N-[(2-naphthyl)methylidene]-2-methyl-2-propanesulfinamide (507469-91-2) → (RS,2R,3S)-2-fluoro-3-(2-methylpropane-2-sulfinylamino)-3-naphthalen-2-ylpropionic acid methyl ester

Conditions	Yield
With N,N,N,N,-tetramethylethylenediamine; lithium hexamethyldisilazane In tetrahydrofuran at -70℃; for 0.5h; Inert atmosphere; diastereoselective reaction;	70%
With potassium hexamethylsilazane In tetrahydrofuran; N,N-dimethyl-formamide at -40℃; for 0.5h; Inert atmosphere;	n/a

methyl fluoroacetate (453-18-9) + N-t-butylsulfinyl-2-pyridinyl carboxaenamine (1015198-59-0) → (RS,2R,3S)-2-fluoro-3-(2-methylpropane-2-sulfinylamino)-3-pyridin-2-ylpropionic acid methyl ester + C13H19FN2O3S

Conditions	Yield
With N,N,N,N,-tetramethylethylenediamine; lithium hexamethyldisilazane In tetrahydrofuran at -70℃; for 0.5h; Inert atmosphere; diastereoselective reaction;	A 70% B n/a

1-indoline (496-15-1) + methyl fluoroacetate (453-18-9) → 2-fluoro-1-(indolin-1-yl)ethanone

Conditions	Yield
at 80℃; for 12h;	70%

Dimethyl oxalate (553-90-2) + methyl fluoroacetate (453-18-9) + O-methylisourea hemisulfate (52328-05-9) → C7H7FN2O4

Conditions	Yield
Stage #1: Dimethyl oxalate; methyl fluoroacetate With sodium methylate In toluene at 25℃; for 2h; Stage #2: O-methylisourea hemisulfate With sodium methylate In toluene at 35℃; for 8h;	70%

methyl fluoroacetate (453-18-9) + allyl 6-O-(5-amino-3,5-dideoxy-α-D-neuraminopyranosyl)-2-amino-2-deoxy-α-D-galactopyranoside → C22H34F2N2O14 (1263481-00-0)

Conditions	Yield
With triethylamine In methanol at 20℃; Inert atmosphere; Cooling with ice;	67%

methyl fluoroacetate (453-18-9) + trans-4-[2-(4-benzo[1,3]dioxol-4-yl-piperidin-1-yl)ethyl]cyclohexylamine hydrochloride → trans-N-{4-[2-(4-benzo[1,3]dioxol-4-ylpiperidin-1-yl)ethyl]cyclohexyl}-2-fluoroacetamide

Conditions	Yield
Stage #1: methyl fluoroacetate With potassium trimethylsilonate In 1,4-dioxane at 20℃; Stage #2: trans-4-[2-(4-benzo[1,3]dioxol-4-yl-piperidin-1-yl)ethyl]cyclohexylamine hydrochloride With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In 1,4-dioxane at 20℃; for 4h;	66.7%

methyl fluoroacetate (453-18-9) + trans-4-[2-(4-benzo[1,3]dioxol-4-yl-piperidin-1-yl)-ethyl]-cyclohexylamine hydrochloride → N-trans-{4-[2-(4-benzo[1,3]dioxol-4-yl-piperidin-1-yl)-ethyl]-cyclohexyl}-2-fluoro-acetamide (1395922-18-5)

Conditions	Yield
Stage #1: methyl fluoroacetate With potassium trimethylsilonate In 1,4-dioxane at 20℃; Stage #2: trans-4-[2-(4-benzo[1,3]dioxol-4-yl-piperidin-1-yl)-ethyl]-cyclohexylamine hydrochloride With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In 1,4-dioxane at 20℃; for 4h;	66.7%

Upstream product

• 67-56-1 methanol 
• 640-19-7 fluoroacetamide 
• 96-34-4 methyl chloroacetate 
• 96-32-2 bromoacetic acid methyl ester 
• 116-15-4 perfluoropropylene 
• 359-06-8 monofluoroacetyl chloride 
• 557-31-3 3-ethoxyprop-1-ene 
• 181224-33-9 Methyl fluoroiodoacetate 
• 292638-85-8 acrylic acid methyl ester 
• 77-78-1 dimethyl sulfate 
• 64-17-5 ethanol 
• 107-13-1 acrylonitrile 
• 5199-50-8 methyl 2-iodoacetate 

Downstream Products

• 337-72-4 2-fluoro-1,1-diphenylethan-1-ol 
• 2294-93-1 1,2,2-triphenyl-1-ethanol 
• 363-59-7 dimethyl α,α'-difluorosuccinate 
• 371-62-0 2-fluoroethanol 
• 144-49-0 Fluoroacetic acid 
• 640-19-7 fluoroacetamide 
• 392-64-3 2,4-difluoro-acetoacetic acid methyl ester 
• 370-07-0 2-fluoro-3-phenyl acrylic acid methyl ester 
• 325-85-9 fluoro-acetic acid dibutylamide 
• 366-38-1 2-fluoro-1-morpholin-4-ylethanone 
• 325-57-5 N-Fluoracetyl-piperidin 
• 1480-96-2 2-methoxy-5-fluorouracil 
• 344-14-9 dimethyl 2-fluoromalonate 
• 62-74-8 sodium fluoroacetate 

Relevant articles and documents

Analyse structurale des derives fonctionnels des acides carboxyliques. Partie II. Halogeno et cyanoacetates de methyle

Methylene bending mode analysis and dipole moment determinations were carried out in solution (CCl4) for some methyl esters ΣCH2CO2Me with Σ =F(I), Cl(II), Br(III), I(IV), CN(V), in order to identify the conformers induced by ΣCH2 group rotating motion and determine their relation amounts.The results are consistent with the existence of two conformations; syn and anti for (I), syn and gauche for (II) and (III).Compounds (IV) and (V) occur almost exclusively in gauche and syn forms respectively.A theoretical study of compounds (I), (II) and (V) by P.C.I.L.O. methods and the Onsager formalism was performed.The collected data show that the conformers have the O-Me bond syn to the carbonyl.The calculated value of ΔE for the equilibrium between the syn and anti rotamers (Ea-Es =600 cal mol-1) is in good agreement with ΔH0298 estimated from the temperature-dependence studies (ΔE =158 cal mol-1).

Novel and practical preparation of α-fluoro-functionalized esters from fluoroiodoacetates

The addition reaction of fluoroiodoacetates 2 to various electron-rich alkenes 3 initiated by iron powder in dry THF at 70-80°C gave 1:1 adducts 4 in good yields. A variety of functionalities in the alkenes such as trimethylsilyl, alkoxy, acetoxy, hydroxy and ester could be tolerated under the reaction conditions. Reduction of the adducts 4 with Zn-AcOH in ethanol or Zn-NiCl2·OH2O in moist THF was readily accomplished, and the overall procedure was amenable to a convenient one-flask procedure. Treatment of fluoroiodoacetates 2 with electron-deficient alkenes 7 in the presence of an Fe-CrCl3·OH2O-bpy bimetal redox system in ethanol at 70-80°C resulted in the formation of iodine-free 1:1 adducts 8 in moderate to good yields. It is proposed that the addition reactions of fluoroiodoacetates 2 to electronrich and electron-deficient alkenes proceeded through a single-electron-transfer mechanism.