454-31-9

Basic information

• Product Name: Ethyl difluoroacetate
• Synonyms: difluoro-aceticaciethylester;DIFLUOROACETIC ACID ETHYL ESTER;ETHYL DIFLUOROACETATE;ETHYL DIFLUOROACETIC ACID;ART-CHEM-BB B020251;AKOS B020251;ETHYL DIFLUOROACETATE 97%;Ethyldifluoroacetate,98%
• CAS NO: 454-31-9
• Molecular Formula: C₄H₆F₂O₂
• Molecular Weight: 124.09
• EINECS: 207-223-4
• Product Categories: Pharmaceutical Intermediates;Fluoro-Aliphatics ;Organic Fluorides;Fluorochemicals;Fluorinated Building Blocks;Fluorinating Reagents & Building Blocks for Fluorinated Biochemical Compounds;Synthetic Organic Chemistry;C2 to C5;Carbonyl Compounds;Esters
• Mol File: 454-31-9.mol
• Article Data: 36

Chemical Properties

• Boiling Point: 97 °C
• Flash Point: 25 °C
• Appearance: Clear colorless/Liquid
• Density: 1.242
• Vapor Pressure: 0.836mmHg at 25°C
• Refractive Index: 1.3465-1.3485
• Storage Temp.: 2-8°C
• Solubility: DMSO (Sparingly), Methanol (Sparingly)
• Water Solubility: Slightly soluble in water
• BRN: 1748597
• CAS DataBase Reference: Ethyl difluoroacetate(CAS DataBase Reference)
• NIST Chemistry Reference: Ethyl difluoroacetate(454-31-9)
• EPA Substance Registry System: Ethyl difluoroacetate(454-31-9)

Safety Data

• Hazard Codes: C,F,T,Xi
• Statements: 34-10
• Safety Statements: 45-36/37/39-26-16-27
• RIDADR: 1992
• WGK Germany: 3
• TSCA: Yes
• HazardClass: 3
• PackingGroup: III
• Hazardous Substances Data: 454-31-9(Hazardous Substances Data)

Usage

Chemical Properties

clear colorless liquid

Uses

Ethyl difluoroacetate is used in pharmaceutical intermediates, acrylization oxidation and halogenating reaction of catalyst. Also ethyl difluoroacetate is used in preparing pyrrazolo-pyrimidine derivatives.

General Description

Ethyl difluoroacetate was degraded to difluoroacetic acid by the strains of Actinobacteria.

InChI:InChI=1/C7H11F3O/c8-7(9,10)5-2-1-3-6(11)4-5/h5-6,11H,1-4H2

Synthetic route

Ethyl bromodifluoroacetate (667-27-6) → ethyl difluoroacetate (454-31-9)

Conditions	Yield
With 1,3-dimethyl-2-phenyl-2,3-dihydro-1H-7-methylbenzo-[d]imidazole; [Zr(2,6-bis(5-methyl-3-phenyl-1H-pyrrol-2-yl)pyridine)2] In benzene-d6 for 2.5h; Catalytic behavior; UV-irradiation; Inert atmosphere; Schlenk technique;	98%
With 1,2,3-trimethoxybenzene; (3,5-dimethyl-2-(2-pyridyl)pyrrolide)3ZrCl; 1,3-dimethyl-2-phenyl-2,3-dihydro-1H-7-methylbenzo-[d]imidazole In benzene-d6 at 33℃; for 0.5h; Time; Irradiation; Glovebox;	85%
With N,N,N,N,-tetramethylethylenediamine In dimethylsulfoxide-d6 at 20℃; for 15h; Irradiation;	41%
Stage #1: Ethyl bromodifluoroacetate With zinc In tetrahydrofuran at 20 - 50℃; for 1h; Inert atmosphere; Stage #2: With hydrogenchloride In tetrahydrofuran; water at 0℃; Product distribution / selectivity;	~ 90 %Chromat.
With hydrogen; nickel; triethylamine In ethanol at 80℃; under 3750.38 - 7500.75 Torr;

ethanol (64-17-5) + 2,2-difluoroacetyl fluoride (2925-22-6) → ethyl difluoroacetate (454-31-9)

Conditions	Yield
With N,N-dimethyl acetamide for 4h; Product distribution / selectivity; Inert atmosphere; Sealed tube; Cooling with ice;	96%
With sodium carbonate at 5 - 20℃; for 1h; Product distribution / selectivity; Inert atmosphere;	77%
at 20℃; for 0.5h;

ethanol (64-17-5) + Difluoroacetic acid N,N-dimethylamide (667-50-5) → ethyl difluoroacetate (454-31-9)

Conditions	Yield
With sulfuric acid at 0 - 70℃; for 2h; Temperature;	93.98%

1,1-diethoxy-2,2-difluoro-ethane (36589-84-1) → ethyl difluoroacetate (454-31-9)

Conditions	Yield
With dihydrogen peroxide; vanadia at 5℃; for 5h;	89.9%

1,1,2,2-tetrafluoroethyl ethyl ether (512-51-6) → ethyl difluoroacetate (454-31-9)

Conditions	Yield
With sulfuric acid In water at 54 - 56℃; for 1h;	87%
Stage #1: Ethyl 1,1,2,2-tetrafluoroethyl ether With sulfuric acid; hydrogen fluoride In ethanol; water at -20 - 50℃; for 24h; Autoclave; Stage #2: With sodium hydrogencarbonate at 20℃; under 760.051 Torr; for 1h; Reagent/catalyst;	86%
With nitric acid
With sulfuric acid
With water; fluorinated γ-alumina at 180℃; for 0.0202778h; Product distribution / selectivity; Inert atmosphere; Gas phase;

ethanol (64-17-5) + 1,1,2,2-tetrafluoroethyl ethyl ether (512-51-6) → ethyl difluoroacetate (454-31-9)

Conditions	Yield
With sulfuric acid; silica gel at 50℃; for 24h; Time; Autoclave;	86%

ethyl 2-chloro-2,2-difluoroacetate (383-62-0) → ethyl difluoroacetate (454-31-9)

Conditions	Yield
With palladium on activated charcoal; hydrogen; triethylamine In ethanol at 30℃; under 750.075 - 3000.3 Torr;	75%
With zinc In N,N-dimethyl-formamide at 70℃; Yield given;

1-Heptene (592-76-7) + ethyl 2,2-difluoro-2-iodoacetate (7648-30-8) → ethyl difluoroacetate (454-31-9) + Ethyl 2,2-Difluoro-4-iodononanoate (127224-10-6)

Conditions	Yield
With hydroquinone; nickel dichloride; zinc In tetrahydrofuran; water 1) RT, 15 min, 2) RT, 20 min;	A 70% B 17%

ethyl 2-chloro-2,2-difluoroacetate (383-62-0) → Difluoroacetic acid (381-73-7) + ethyl difluoroacetate (454-31-9) + 2-chloro-2,2-difluoroacetic acid (76-04-0)

Conditions	Yield
With ethanol; zinc for 1 - 3h; Product distribution / selectivity; Heating / reflux;	A 9.7% B 61.6% C 0.4%

ethanol (64-17-5) + difluoroacetonitrile (359-12-6) → ethyl difluoroacetate (454-31-9)

Conditions	Yield
With sulfuric acid In water at 10 - 120℃; for 14h;	57%

2-oxo-propionic acid ethyl ester (617-35-6) + Ethyl bromodifluoroacetate (667-27-6) → ethyl difluoroacetate (454-31-9) + 2,2,3,3-tetrafluoro-4-hydroxy-4-methyl-pentanedioic acid diethyl ester

Conditions	Yield
Stage #1: 2-oxo-propionic acid ethyl ester; Ethyl bromodifluoroacetate In N,N-dimethyl-formamide at -20℃; Stage #2: With Tetrakis(dimethylamino)ethylen In N,N-dimethyl-formamide at -20 - 20℃;	A n/a B 25%

Ethyl bromodifluoroacetate (667-27-6) + 1,3,5-tris(4-methoxybenzyl)hexahydro-1,3,5-triazine (58837-16-4) → ethyl difluoroacetate (454-31-9) + 1-(4'-methoxybenzyl)-3,3-difluoroazetidin-2-one + 3,3,5,5-tetrafluoro-1-(4-methoxy-benzyl)-piperidine-2,4-dione + 5,5-difluoro-1,3-bis-(4-methoxy-benzyl)-tetrahydro-pyrimidin-4-one

Conditions	Yield
Stage #1: Ethyl bromodifluoroacetate With chloro-trimethyl-silane; zinc In tetrahydrofuran for 0.416667h; Stage #2: 1,3,5-tris(4-methoxybenzyl)hexahydro-1,3,5-triazine In tetrahydrofuran at 25℃; for 3h;	A n/a B 25% C n/a D n/a

ethyl 1,1-dichloroacetate (535-15-9) → ethyl difluoroacetate (454-31-9)

Conditions	Yield
With potassium fluoride In ethanol; water at 100℃; for 40h; Solvent; Concentration;	21%
With potassium fluoride; C6H9BO4 In ISOPROPYLAMIDE at 20 - 75℃; Halex reaction;

chloro-trimethyl-silane (75-77-4) + ethyl trifluoroacetate, (383-63-1) → ethyl difluoroacetate (454-31-9) + α-(trimethylsilyl)difluoroacetic acid ethyl ester (205865-67-4) + trifluoroacetyltrimethylsilane ethyltrimethylsilyl ketal (565214-84-8) + 2,3-diethoxy-1,1,1,4,4,4-hexafluoro-2,3-bis-trimethylsilanyloxy-butane

Conditions	Yield
With tetrabutylammomium bromide In tetrahydrofuran at -25℃; Electrochemical reaction; Further byproducts given;	A 8% B 8 % Spectr. C 33 % Spectr. D 1 % Spectr.

Difluoroacetic acid (381-73-7) + ethanol (64-17-5) → ethyl difluoroacetate (454-31-9)

Conditions	Yield
With sulfuric acid

acetyl fluoride (557-99-3) → ethyl difluoroacetate (454-31-9)

Conditions	Yield
With fluorine at 100℃; ueber Kupferdrahtnetz und Umsetzen der Reaktionsprodukte mit absol.Aethanol;

diazomethane (186581-53-3, 908094-01-9) + diethyl ether (60-29-7) + 1,1,2,3,4,4-hexafluoro-2-butene (17976-35-1) → difluoroacetic acid methyl ester (433-53-4) + ethyl difluoroacetate (454-31-9)

Conditions	Yield
With potassium hydroxide; potassium permanganate 1.) 60 degC, water; Yield given. Multistep reaction. Yields of byproduct given;

Difluoroacetic acid (381-73-7) + sodium ethanolate (141-52-6) → ethyl difluoroacetate (454-31-9)

Conditions	Yield
With N-(2-chloro-1,1,2-trifluoroethyl)diethylamine; sodium fluoride 1.) -78 deg C, 15 min, 2.) triglyme; Yield given. Multistep reaction;

ethyl trifluoroacetate, (383-63-1) → ethane (74-84-0) + Fluoroacetic acid (144-49-0) + ethyl 2-fluoroacetate (459-72-3) + ethyl difluoroacetate (454-31-9) + ethyl acetate (141-78-6)

Conditions	Yield
With N,N,N,N,N,N-hexamethylphosphoric triamide for 2h; Quantum yield; Irradiation;

1,1,2,2-tetrafluoroethyl ethyl ether (512-51-6) + sulfuric acid (7664-93-9) → ethyl difluoroacetate (454-31-9)

diethyl sulfate (64-67-5) + difluoroacetate_of sodium → ethyl difluoroacetate (454-31-9)

acetyl fluoride (557-99-3) + fluorine + copper wire → ethyl 2-fluoroacetate (459-72-3) + ethyl difluoroacetate (454-31-9) + ethyl trifluoroacetate, (383-63-1)

Conditions	Yield
at 100℃; Umsetzen der Reaktionsprodukte mit absol.Aethanol bei -80grad,zuletzt bei Siedetemperatur;

N-benzylidene benzylamine (780-25-6) + α-(trimethylsilyl)difluoroacetic acid ethyl ester (205865-67-4) → ethyl difluoroacetate (454-31-9) + N-benzylidene-α-(trimethylsilyl)benzylamine (53986-95-1)

Conditions	Yield
With N,N,N,N,N,N-hexamethylphosphoric triamide; potassium fluoride at 50℃; for 12h;

Ethyl bromodifluoroacetate (667-27-6) + ethyl acrylate (140-88-5) → ethyl difluoroacetate (454-31-9) + 2,2-difluoroglutaric acid diethyl ester (428-97-7)

Conditions	Yield
With N,N,N,N,-tetramethylethylenediamine; water; copper In tetrahydrofuran Michael Addition;	A 10 %Spectr. B 52 %Spectr.

Ethyl bromodifluoroacetate (667-27-6) + phenylboronic acid (98-80-6) → ethyl difluoroacetate (454-31-9) + ethyl 2,2-difluoro-2-phenylacetate (2248-46-6)

Conditions	Yield
With 2,2':6,2''-terpyridine; nickel chloride dimethyl ether; potassium carbonate In 1,4-dioxane at 80℃; for 8h; Schlenk technique; Inert atmosphere;	A 7 %Spectr. B 1 %Spectr.
With [2,2]bipyridinyl; [1,1'-bis(diphenylphosphino)ferrocene]nickel(II) chloride; potassium carbonate In 1,4-dioxane at 80℃; for 8h; Reagent/catalyst; Solvent; Schlenk technique; Inert atmosphere;	A 6 %Spectr. B 89 %Spectr.

1-ethenyl-2-pyrrolidinone (88-12-0) + Ethyl bromodifluoroacetate (667-27-6) + 4-biphenylboronic acid (5122-94-1) → ethyl difluoroacetate (454-31-9) + ethyl 4-([1,1'-biphenyl]-4-yl)-2,2-difluoro-4-(2-oxopyrrolidin-1-yl)butanoate + 2-([1,1'-biphenyl]-4-yl)-2,2-difluoroacetic acid ethyl ester (73789-98-7)

Conditions	Yield
With (1,2-dimethoxyethane)dichloronickel(II); 4,4'-dibromo-2,2'-bipyridine; potassium carbonate In tetrahydrofuran at 80℃; for 24h; Reagent/catalyst; Solvent; Schlenk technique; Inert atmosphere;	A 15 %Spectr. B 53 %Spectr. C 13 %Spectr.

1-ethenyl-2-pyrrolidinone (88-12-0) + Ethyl bromodifluoroacetate (667-27-6) + 4-biphenylboronic acid (5122-94-1) → ethyl difluoroacetate (454-31-9) + ethyl 4-([1,1'-biphenyl]-4-yl)-2,2-difluoro-4-(2-oxopyrrolidin-1-yl)butanoate + C10H13F2NO3 + 2-([1,1'-biphenyl]-4-yl)-2,2-difluoroacetic acid ethyl ester (73789-98-7)

Conditions	Yield
With bis(triphenylphosphine)nickel(II) chloride; 4,4'-Dimethoxy-2,2'-bipyridin; potassium carbonate In tetrahydrofuran at 80℃; for 24h; Concentration; Reagent/catalyst; Solvent; Schlenk technique; Inert atmosphere;	A 13 %Spectr. B 49 %Spectr. C 7 %Spectr. D 36 %Spectr.

ethyl 2-chloro-2,2-difluoroacetate (383-62-0) → difluoroethanol (359-13-7) + ethyl difluoroacetate (454-31-9)

Conditions	Yield
With palladium on activated charcoal; hydrogen; triethylamine In ethanol at 45℃; under 7500.75 - 30003 Torr; for 5h; Temperature; Time; Pressure;

ethyl 2,2-difluoro-2-iodoacetate (7648-30-8) → ethyl difluoroacetate (454-31-9)

Conditions	Yield
With palladium on activated charcoal; hydrogen; triethylamine In tetrahydrofuran at 100℃; under 750.075 - 15001.5 Torr;
With diethylzinc In hexane; [D3]acetonitrile at -20℃; for 8h; Schlenk technique; Inert atmosphere;

ethyl difluoroacetate (454-31-9) → 1-ethoxy-2,2-difluoroethanol (148992-43-2)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran; diethyl ether at -78℃; for 2.75h;	100%
With lithium aluminium tetrahydride In tetrahydrofuran; diethyl ether at -78℃; for 3h;	60%
With lithium aluminium tetrahydride In tetrahydrofuran; diethyl ether at -78℃; for 3h; Reagent/catalyst; Solvent;	60%

ethyl difluoroacetate (454-31-9) + D-mannosamine (90-76-6, 90-77-7, 530-23-4, 579-32-8, 579-33-9, 643-68-5, 2596-19-2, 6490-68-2, 6490-70-6, 6490-72-8, 6490-73-9, 6490-74-0, 14196-84-0, 14196-86-2, 14257-69-3, 58381-21-8) → N-difluoroacetyl-D-mannosamine

Conditions	Yield
In methanol at 20℃; for 16h;	100%

ethyl difluoroacetate (454-31-9) + C13H23NO3 → C15H23F2NO4

Conditions	Yield
With potassium tert-butylate In toluene at 0 - 20℃; for 2h; Inert atmosphere;	100%
With potassium tert-butylate In toluene at 0 - 20℃; for 2h; Inert atmosphere;	100%
With potassium tert-butylate In toluene at 0 - 20℃; Inert atmosphere;	100%
With potassium tert-butylate In toluene at 0 - 20℃; for 2h; Inert atmosphere;	100%

ethyl difluoroacetate (454-31-9) + C13H23NO3 → C15H23F2NO4

Conditions	Yield
With potassium tert-butylate In toluene at 0 - 20℃; for 2h; Inert atmosphere;	100%

(S)-{(1α,5α,6α)-3-[4-(5-aminomethyl-2-oxooxazolidin-3-yl)-2,6-difluorophenyl]-3-azabicyclo[3.1.0]hex-6-yl}carbamic acid tert-butyl ester (681425-32-1) + ethyl difluoroacetate (454-31-9) → (S)-[(1α,5α,6α)-3-(4-{5-[(2,2-difluoroacetylamino)methyl]-2-oxooxazolidin-3-yl}-2,6-difluorophenyl)-3-azabicyclo[3.1.0]hex-6-yl]carbamic acid tert-butyl ester (681425-33-2)

Conditions	Yield
With triethylamine In methanol at 20℃; for 15h;	99%
With triethylamine In methanol at 20℃; for 15h;	99%

ethyl difluoroacetate (454-31-9) + 5-(aminomethyl)-2-chloropyridine (97004-04-1) → N-(2-chloro-5-aminomethylpyridine)-1,1-difluoroacetamide (1135440-09-3)

Conditions	Yield
at 100℃; for 1h; Reflux;	99%

ethyl difluoroacetate (454-31-9) + trifluoroacetic acid (76-05-1) → Difluoroacetic acid (381-73-7) + ethyl trifluoroacetate, (383-63-1)

Conditions	Yield
at 85℃; Product distribution / selectivity;	A 99% B n/a

ethyl difluoroacetate (454-31-9) + C14H23NO3 → C16H23F2NO4

Conditions	Yield
With potassium tert-butylate In toluene at 0 - 20℃; for 2h; Inert atmosphere;	99%
With potassium tert-butylate In toluene at 0 - 20℃; Inert atmosphere;	99%

ethyl difluoroacetate (454-31-9) + C13H22FNO3 → C15H22F3NO4

Conditions	Yield
With potassium tert-butylate In toluene at 0 - 20℃; Inert atmosphere;	99%

chloro-trimethyl-silane (75-77-4) + benzophenone (119-61-9) + ethyl difluoroacetate (454-31-9) → diphenylmethyl trimethylsilyl ether (14629-59-5)

Conditions	Yield
With magnesium In 1-methyl-pyrrolidin-2-one at 20℃; Inert atmosphere;	98%

tert-butyl 3-acetylpiperidine-1-carboxylate (858643-92-2) + ethyl difluoroacetate (454-31-9) → tert-butyl 3-(4,4-difluoro-3-oxobutanoyl)piperidine-1-carboxylate

Conditions	Yield
With potassium tert-butylate In benzene at 0 - 20℃; for 5h; Inert atmosphere;	98%
With potassium tert-butylate In benzene at 0 - 20℃; for 5h; Inert atmosphere;	97%

ethyl difluoroacetate (454-31-9) + phenethylamine (64-04-0) → 2,2-difluoro-N-(2-phenylethyl)acetamide

Conditions	Yield
In dichloromethane for 16h; Reflux; Inert atmosphere;	98%

ethyl difluoroacetate (454-31-9) + histamine (51-45-6) → 2,2-difluoro-N-[2-(1H-imidazol-4-yl)ethyl]acetamide

Conditions	Yield
In dichloromethane for 16h; Reflux; Inert atmosphere;	98%

ethyl difluoroacetate (454-31-9) + 5-acetyl-6-hydroxy-4,7-dimethoxybenzofuran (484-51-5) → 7-(difluoromethyl)-7-hydroxy-4,9-dimethoxy-6,7-dihydro-5H-furo[3,2-g]chromen-5-one (376384-40-6)

Conditions	Yield
With lithium hydride In tetrahydrofuran Heating;	97%

ethyl difluoroacetate (454-31-9) + Diethyl methylphosphonate (683-08-9) → diethyl (3,3-difluoro-2-oxopropyl)phosphonate (1023327-32-3)

Conditions	Yield
Stage #1: Diethyl methylphosphonate With n-butyllithium In tetrahydrofuran; hexane at -95℃; for 1h; Inert atmosphere; Stage #2: ethyl difluoroacetate In tetrahydrofuran; hexane at -95 - -90℃; for 1h; Inert atmosphere;	97%
Stage #1: Diethyl methylphosphonate With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 1h; Stage #2: ethyl difluoroacetate In tetrahydrofuran at -78 - 0℃; Further stages.;	82%
With n-butyllithium In tetrahydrofuran; hexane at -78 - -65℃; for 3h;

ethyl difluoroacetate (454-31-9) → 2,2-difluoroacetamide (359-38-6)

Conditions	Yield
With ammonia In ethanol at 0 - 25℃; for 2.5h;	96%
With ammonia

ethyl difluoroacetate (454-31-9) + 1-(3-fluoro-4-methoxyphenyl)ethanone (455-91-4) → 4,4-difluoro-1-(3-fluoro-4-methoxyohenyl)-butane-1,3-dione (170570-77-1)

Conditions	Yield
With hydrogenchloride; sodium methylate In tert-butyl methyl ether	96%
With hydrogenchloride; sodium methylate In tert-butyl methyl ether	96%
With hydrogenchloride; sodium methylate In tert-butyl methyl ether	96%

formic acid (64-18-6) + ethyl difluoroacetate (454-31-9) → Difluoroacetic acid (381-73-7) + formic acid ethyl ester (109-94-4)

Conditions	Yield
sulfuric acid at 70℃; Product distribution / selectivity;	A 96% B n/a

ethyl difluoroacetate (454-31-9) + ethyl acetate (141-78-6) → ethyl 4,4-difluoro-3-oxobutyrate (352-24-9)

Conditions	Yield
Stage #1: ethyl acetate With sodium ethanolate at 25℃; Stage #2: ethyl difluoroacetate at 10 - 65℃; Stage #3: With sulfuric acid; water at 20 - 25℃; for 0.333333h; Product distribution / selectivity;	95.5%
With multielement hydrotalcite at 55℃; for 8h; Catalytic behavior; Temperature; Reagent/catalyst; Green chemistry;	88.9%
With lithium diisopropyl amide In diethyl ether at -70℃; for 4h;	82%

ethyl difluoroacetate (454-31-9) + phenylacetylene (536-74-3) → 1,1-difluoro-4-phenyl-3-butyn-2-one (117710-72-2)

Conditions	Yield
Stage #1: phenylacetylene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 3h; Inert atmosphere; Stage #2: ethyl difluoroacetate With boron trifluoride diethyl etherate In tetrahydrofuran; hexane at -78℃; for 2h; Inert atmosphere;	95%
With n-butyllithium; boron trifluoride diethyl etherate 1.) THF, -78 deg C, 30 min, 2.) -78 deg C, 90 min; Yield given. Multistep reaction;
With n-butyllithium; boron trifluoride diethyl etherate 1.) hexane, THF, -78 deg C, 30 min, 2.) THF, hexane, -78 deg C, 1.5 h; Yield given. Multistep reaction;
With n-butyllithium; boron trifluoride diethyl etherate

benzoimidazole (51-17-2) + ethyl difluoroacetate (454-31-9) → 1-(difluoromethyl)-1H-benzo[d]imidazole (84941-15-1)

Conditions	Yield
With potassium hydroxide In acetonitrile at 60℃; for 6h; Concentration; Solvent; Temperature; Sealed tube;	95%

ethyl difluoroacetate (454-31-9) → difluoroethanol (359-13-7)

Conditions	Yield
With hydrogen at 110℃; under 3750.38 - 15001.5 Torr; for 4h; Temperature; Pressure; Autoclave;	93.3%
With C39H53ClN2P2Ru; potassium methanolate; hydrogen In tetrahydrofuran at 20℃; under 38002.6 Torr; for 16h; Glovebox; Autoclave;	93%
With lithium aluminium tetrahydride In tetrahydrofuran at -10℃; for 1h;	44.6%

ethyl difluoroacetate (454-31-9) + 1-(2-anilinophenyl)ethan-1-one (23699-74-3) → 2-(difluoromethyl)-1-phenylquinolin-4(1H)-one (837364-34-8)

Conditions	Yield
With lithium hydride In tetrahydrofuran for 1h; Heating;	93%

ethyl difluoroacetate (454-31-9) + 4'-benzyloxy-acetophenone (54696-05-8) → 4,4-difluoromethyl-1-(4-benzyloxyphenyl)-butane-1,3-dione

Conditions	Yield
With sodium methylate In methanol	93%

ethyl difluoroacetate (454-31-9) + 1-cyclohexenyl methyl ketone (932-66-1) → 4,4-difluoro-1-[2-cyclohexenyl]-butane-1,3-dione

Conditions	Yield
With hydrogenchloride; sodium methylate	93%
With hydrogenchloride; sodium methylate	93%

ethyl difluoroacetate (454-31-9) + C10H11FN2O → C12H11F3N2O2

Conditions	Yield
With dmap In methanol at 20℃; for 12h;	92.8%

Upstream product

• 557-99-3 acetyl fluoride 
• 512-51-6 Ethyl 1,1,2,2-tetrafluoroethyl ether 
• 186581-53-3 diazomethane 
• 60-29-7 diethyl ether 
• 17976-35-1 1,1,2,3,4,4-hexafluoro-2-butene 
• 592-76-7 1-Heptene 
• 7648-30-8 ethyl 2,2-difluoro-2-iodoacetate 
• 383-63-1 ethyl trifluoroacetate, 
• 383-62-0 ethyl 2-chloro-2,2-difluoroacetate 
• 7664-93-9 sulfuric acid 
• 64-67-5 diethyl sulfate 
• 780-25-6 N-benzylidene benzylamine 
• 205865-67-4 α-(trimethylsilyl)difluoroacetic acid ethyl ester 
• 667-27-6 Ethyl bromodifluoroacetate 

Downstream Products

• 372-31-6 ethyl 4,4,4-trifluoroacetoacetate 
• 49648-37-5 Difluoroacetyl D-threo amphenicol 
• 788-54-5 1,1-bis-(4-bromo-phenyl)-2,2-difluoro-ethanol 
• 337-53-1 1,1-Difluoro-2-hydroxy-2,2-diphenylethane 
• 352-24-9 ethyl 4,4-difluoro-3-oxobutyrate 
• 359-38-6 2,2-difluoroacetamide 
• 145299-84-9 1,1-difluoro-4-phenyl-butan-2-one 
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• 134731-37-6 4,4-difluoro-1-[4-(methylthio)phenyl]-butane-1,3-dione 
• 170570-77-1 4,4-difluoro-1-(3-fluoro-4-methoxyohenyl)-butane-1,3-dione 
• 62679-61-2 4,4-difluoro-1-phenyl-1,3-butanedione 

Relevant articles and documents

Tandem Difluoroalkylation-Arylation of Enamides Catalyzed by Nickel

A nickel-catalyzed three-component reaction for the synthesis of difluoroalkylated compounds through tandem difluoroalkylation-arylation of enamides has been developed. The reaction tolerates a variety of arylboronic acids and widely available difluoroalkyl bromides, and even the relatively inert substrate chlorodifluoroacetate. The significant advantages of this protocol are the low-cost nickel catalyst, synthetic convenience, excellent functional-group compatibility and high reaction efficiency.

Access to α,α-Difluoro-γ-amino Acids by Nickel-Catalyzed Reductive Aryldifluoroacetylation of N -Vinylacetamide

A nickel-catalyzed reductive aryldifluoroacetylation of N -vinylacetamide with ethyl chloro(difluoro)acetate and aryl iodides is described. This chelating amide carbonyl group-assisted strategy provides rapid access to a variety of protected α,α-difluoro-γ-amino acids that might have potential applications in peptide chemistry and protein engineering. An advantage of this method is its synthetic simplicity, with no preparation of organometallic reagents.

trans-Selective Aryldifluoroalkylation of Endocyclic Enecarbamates and Enamides by Nickel Catalysis

Efficient methods for the dicarbofuntionalization of the cyclic alkenes 2-pyrroline and 2-azetine are limited. Particularly, the dicarbofunctionalization of endocyclic enecarbamates to achieve fluorinated compounds remains an unsolved issue. Reported here is a nickel-catalyzed trans-selective dicarbofunctionalization of N-Boc-2-pyrroline and N-Boc-2-azetine, a class of endocyclic enecarbamates previously unexplored for transition metal catalyzed dicarbofunctionalization. The reaction can be extended to six- and seven-membered endocyclic enamides. A variety of arylzinc reagents and bromodifluoroacetate, and its derivatives, undergo the reaction, providing straightforward and efficient access to an array of pyrrolidine- and azetidine-containing fluorinated amino acids and oligopeptides, which may have applications in the life sciences.