25597-16-4

Basic information

• Product Name: Ethyl 4,4,4-trifluorocrotonate
• Synonyms: 4.4.4-TRIFLUOROCROTONIC ACID ETHYL ESTER;ETHYL 4,4,4-TRIFLUOROCROTONATE;ETHYL 4,4,4-TRIFLUORO-TRANS-2-BUTENOATE;Ethyl (2E)-4,4,4-trifluoro-2-butenoate;Ethyl 4,4,4-trifluorocrotonate 98%;Ethyl4,4,4-trifluorocrotonate98%;2-Butenoic acid, 4,4,4-trifluoro-, ethyl ester, (2E)-;4,4,4-trifluorocrotonate
• CAS NO: 25597-16-4
• Molecular Formula: C₆H₇F₃O₂
• Molecular Weight: 168.11
• EINECS: -0
• Mol File: 25597-16-4.mol
• Article Data: 29

Chemical Properties

• Boiling Point: 114-115 °C(lit.)
• Flash Point: 78 °F
• Appearance: Clear colorless/Liquid
• Density: 1.125 g/mL at 25 °C(lit.)
• Vapor Pressure: 19.9mmHg at 25°C
• Refractive Index: n20/D 1.3601(lit.)
• Storage Temp.: Flammables area
• BRN: 1707262
• CAS DataBase Reference: Ethyl 4,4,4-trifluorocrotonate(CAS DataBase Reference)
• NIST Chemistry Reference: Ethyl 4,4,4-trifluorocrotonate(25597-16-4)
• EPA Substance Registry System: Ethyl 4,4,4-trifluorocrotonate(25597-16-4)

Safety Data

• Hazard Codes: Xi,F
• Statements: 10-36/37-36/37/38
• Safety Statements: 16-26-27-28-36/37/39-37/39
• RIDADR: UN 3272 3/PG 3
• WGK Germany: 3
• HazardClass: 3
• PackingGroup: III
• Hazardous Substances Data: 25597-16-4(Hazardous Substances Data)

Usage

Chemical Properties

clear colorless liquid

InChI:InChI=1/C6H7F3O2/c1-2-11-5(10)3-4-6(7,8)9/h3-4H,2H2,1H3/b4-3+

Synthetic route

ethyl 3-hydroxy-4,4,4-trifluorobutyrate (372-30-5) → ethyl 4,4,4-trifluorocrotonate (25597-16-4)

Conditions	Yield
With triphenylphosphine; diethylazodicarboxylate In diethyl ether Ambient temperature;	96%
With methanesulfonyl chloride; triethylamine In dichloromethane at -70 - 25℃; for 1h; Reagent/catalyst;	87%
With triethylamine; p-toluenesulfonyl chloride	82%

Togni's reagent II (887144-94-7) + (E)-4-ethoxy-4-oxobut-2-enoic acid (2459-05-4) → ethyl 4,4,4-trifluorocrotonate (25597-16-4)

Conditions	Yield
In N,N-dimethyl-formamide at 120℃; for 24h; Sealed tube; stereoselective reaction;	93%

ethyl 4,4,4-trifluoroacetoacetate (372-31-6) → ethyl 4,4,4-trifluorocrotonate (25597-16-4)

Conditions	Yield
Stage #1: ethyl 4,4,4-trifluoroacetoacetate With sodium tetrahydroborate In diethyl ether Stage #2: With phosphorus pentoxide In diethyl ether	70%
Multi-step reaction with 2 steps 1: 94 percent / sodium borohydride / toluene / 4.5 h / 20 °C 2: 69 percent / phosphorus pentoxide / 1 h View Scheme

ethanol (64-17-5) + 3-(trifluoromethyl)acrylic acid (406-94-0, 130130-81-3, 71027-02-6) → ethyl 4,4,4-trifluorocrotonate (25597-16-4)

Conditions	Yield
With sulfuric acid Heating;

2,2,2-Trifluoroacetaldehyde (75-90-1) + diethyl malonate (105-53-3) → ethyl 4,4,4-trifluorocrotonate (25597-16-4)

ethyl 3-hydroxy-4,4,4-trifluorobutyrate (372-30-5) → ethyl 4,4,4-trifluorocrotonate (25597-16-4) + ethyl (Z)-β-trifluoromethylacrylate (91600-34-9, 406-10-0, 25597-16-4)

Conditions	Yield
With phosphorus pentaoxide for 1h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

ethyl 3-hydroxy-4,4,4-trifluorobutyrate (372-30-5) → ethyl 4,4,4-trifluorocrotonate (25597-16-4) + ethyl 3,4,4,4-tetrafluorobutyrate (94725-82-3) + 4,4,4-Trifluoro-3-fluorosulfinyloxy-butyric acid ethyl ester (344883-34-7)

Conditions	Yield
With sulfur tetrafluoride; sodium fluoride 1.) steel autoclave; 2.) 20 deg C, 60 h; Yield given. Multistep reaction. Yields of byproduct given;

ethyl 3-hydroxy-4,4,4-trifluorobutyrate (372-30-5) + phosphorus (V)-oxide → ethyl 4,4,4-trifluorocrotonate (25597-16-4)

ethyl 3-hydroxy-4,4,4-trifluorobutyrate (372-30-5) + boroxide → (E)-4,4,4-trifluorobut-2-enoate (406-94-0) + ethyl 4,4,4-trifluorocrotonate (25597-16-4)

Conditions	Yield
at 350℃;

2-ethoxycarbonyl-1-(trifluoromethyl)ethyl pentanoate → ethyl 4,4,4-trifluorocrotonate (25597-16-4)

Conditions	Yield
With sodium carbonate	15.90 g (91%)
With caesium carbonate	13.47 g (87%)
With sodium carbonate	15.90 g (91%)
With caesium carbonate	13.47g (87%)

diethoxyphosphoryl-acetic acid ethyl ester (867-13-0) + 2,2,2-Trifluoroacetaldehyde (75-90-1) → ethyl 4,4,4-trifluorocrotonate (25597-16-4)

Conditions	Yield
Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With triethylamine; lithium bromide In tetrahydrofuran at 20℃; for 0.166667h; Inert atmosphere; Stage #2: 2,2,2-Trifluoroacetaldehyde In tetrahydrofuran at 0 - 20℃; for 1.08333h; Inert atmosphere;

ethyl 4,4,4-trifluorocrotonate (25597-16-4) + diethyl malonate (105-53-3) → Diethyl 2-(ethoxycarbonyl)-3-(trifluoromethyl)glutarate

Conditions	Yield
With lithium diisopropyl amide In tetrahydrofuran; hexane 1.) -78 deg C, 30 min, 2.) r.t., 1 h;	99%
Stage #1: diethyl malonate With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: ethyl 4,4,4-trifluorocrotonate In tetrahydrofuran at 0 - 20℃; Inert atmosphere; Stage #3: With hydrogenchloride; water In tetrahydrofuran Inert atmosphere;

ethyl 4,4,4-trifluorocrotonate (25597-16-4) + N-benzyl-N-(methoxymethyl)-N-[(trimethylsilyl)methyl]amine (93102-05-7) → ethyl (+/-)-(3R,4R)-1-benzyl-4-(trifluoromethyl)pyrrolidine-3-carboxylate (152188-51-7)

Conditions	Yield
With trifluoroacetic acid In dichloromethane for 16h; Inert atmosphere; Reflux;	99%
With trifluoroacetic acid In dichloromethane at 0 - 20℃;	98%
With trifluoroacetic acid In dichloromethane	95%
With trifluoroacetic acid In acetonitrile at 70℃; Continuous flow conditions;	74%

2-methylfuran (534-22-5) + ethyl 4,4,4-trifluorocrotonate (25597-16-4) → C11H13F3O3 (1353275-83-8)

Conditions	Yield
With Cl4SnC2HNOBC6H5CH(CH3)2(C6H5)2CH2C10H7 In dichloromethane at -78℃; for 8h; Diels-Alder reaction; Inert atmosphere; optical yield given as %ee; stereoselective reaction;	99%

ethyl 4,4,4-trifluorocrotonate (25597-16-4) + propiophenone lithium enolate (57204-88-3) → (3R*,4R*)-Ethyl 3-(trifluoromethyl)-4-methyl-5-oxo-5-phenylpentanoate (138690-13-8, 138921-71-8, 138921-72-9)

Conditions	Yield
	98%

ethyl 4,4,4-trifluorocrotonate (25597-16-4) + 1-phenyl-propan-1-one (93-55-0) → (3R*,4R*)-Ethyl 3-(trifluoromethyl)-4-methyl-5-oxo-5-phenylpentanoate (138690-13-8, 138921-71-8, 138921-72-9)

Conditions	Yield
With lithium diisopropyl amide In tetrahydrofuran at -78℃; Product distribution; multistep reaction; diastereoselectivity; other lithium enolates of ketones, esters or amides;	98%
With lithium diisopropyl amide 1) THF, -78 deg C, 2) -78 deg C, 0.5 h; Yield given. Multistep reaction;
With lithium diisopropyl amide In tetrahydrofuran; hexane 1.) -78 deg C, 30 min, 2.) -78 deg C, 0.5 h; Yield given;

nitromethane (75-52-5) + ethyl 4,4,4-trifluorocrotonate (25597-16-4) → 4,4,4-trifluoro-3-(nitromethyl)butyric acid ethyl ester (328-62-1)

Conditions	Yield
With N,N,N',N'-tetramethylguanidine at 20℃; for 13h; Inert atmosphere;	98%
With N,N,N',N'-tetramethylguanidine at 20℃; for 13h;	98%
With lithium diisopropyl amide In tetrahydrofuran; hexane 1.) -78 deg C, 30 min, 2.) -78 deg C to r.t., 6.0 h;	83%
In acetonitrile for 0.5h; Michael addition;	90 % Spectr.

ethyl 4,4,4-trifluorocrotonate (25597-16-4) + Ethyl isobutyrate (97-62-1) → Diethyl 2,2-dimethyl-3-(trifluoromethyl)glutarate

Conditions	Yield
With lithium diisopropyl amide In tetrahydrofuran; hexane 1.) -78 deg C, 30 min, 2.) -78 deg C, 1.0 h;	98%

ethyl 4,4,4-trifluorocrotonate (25597-16-4) + 2,4-Dihydroxybenzaldehyde (95-01-2) → ethyl 6-hydroxy-2-(trifluoromethyl)-2H-chromene-3-carboxylate

Conditions	Yield
With potassium carbonate In DMF (N,N-dimethyl-formamide) at 90℃; for 3h;	98%

ethyl 4,4,4-trifluorocrotonate (25597-16-4) → (RS)-5-(trifluoromethyl)pyrazolidin-3-one (1248565-79-8)

Conditions	Yield
With hydrazine hydrate In ethanol for 18h; Reflux;	98%

ethyl 4,4,4-trifluorocrotonate (25597-16-4) + 3-pentanone lithium enolate (1063719-01-6) → (3R*,4R*)-Ethyl 3-(trifluoromethyl)-4-methyl-5-oxoheptanoate (138852-11-6, 138852-12-7)

Conditions	Yield
diastereoselective Michael addition reactions with other lithium enolates;	97%
	97%

ethyl 4,4,4-trifluorocrotonate (25597-16-4) → (E)-4,4,4-trifluorobut-2-enoate (406-94-0)

Conditions	Yield
With sodium hydroxide In water	96%
With sodium hydroxide In tetrahydrofuran; water for 1.5h; Ambient temperature;	93%
With water; sodium hydroxide In ethanol at 20℃; for 19h;	91%

ethyl 4,4,4-trifluorocrotonate (25597-16-4) + 1-methoxy-1,3-cyclohexadiene (2161-90-2) → Ethyl (1RS,2RS,3SR,4RS)-1-methoxy-3-trifluoromethylbicyclo<2.2.2>oct-5-ene-2-carboxylate (133961-04-3)

Conditions	Yield
With cis-2,3-dichlorobutenedioic acid; 2-tert-Butyl-4-methylphenol In benzene for 96h; Heating;	96%

ethyl 4,4,4-trifluorocrotonate (25597-16-4) + 2-amino-benzenethiol (137-07-5) → ethyl 3-(2-aminophenyl)thio-4,4,4-trifluorobutyrate

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 24h;	95%

ethyl 4,4,4-trifluorocrotonate (25597-16-4) + diethyl malonate (105-53-3) → 3-(trifluoromethyl)pentanedioic acid (4162-55-4)

Conditions	Yield
With hydrogenchloride; potassium hydroxide; tetrabutylammomium bromide In tetrahydrofuran; water; acetic acid	95%

ethyl 4,4,4-trifluorocrotonate (25597-16-4) + bis(pinacol)diborane (73183-34-3) → ethyl 4,4,4-trifluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butanoate

Conditions	Yield
With methanol; copper(l) iodide; potassium carbonate In tetrahydrofuran at 20℃; for 30h; Inert atmosphere; chemoselective reaction;	95%

ethyl 4,4,4-trifluorocrotonate (25597-16-4) + t-butoxycarbonylhydrazine (870-46-2) → 3-(N'-tert-butoxycarbonylhydrazino)-4,4,4-trifluorobutyric acid ethyl ester (1123546-28-0)

Conditions	Yield
In methanol at 70℃; for 72h; Michael condensation;	94%

ethyl 4,4,4-trifluorocrotonate (25597-16-4) + sodium methylate (124-41-4) → 4,4,4-trifluoro-3-methoxybutanoic acid (1343115-14-9)

Conditions	Yield
In methanol at 20℃;	93.8%

ethyl 4,4,4-trifluorocrotonate (25597-16-4) + cyclopentanone (120-92-3) → Ethyl 3-(2'-oxocyclopentyl)-3-(trifluoromethyl)propionate

Conditions	Yield
With lithium diisopropyl amide In tetrahydrofuran; hexane 1.) -78 deg C, 30 min, 2.) -40 deg C, 4.0 h;	93%

ethyl 4,4,4-trifluorocrotonate (25597-16-4) + 3,5-dichlorosalicyclaldehyde (90-60-8) → ethyl 6,8-dichloro-2-(trifluoromethyl)-2H-chromene-3-carboxylate (1160474-53-2)

Conditions	Yield
With triethylamine In dimethyl sulfoxide at 85℃; for 72h;	93%
regiospecific reaction;

ethyl 4,4,4-trifluorocrotonate (25597-16-4) → ethyl 2,3-dibromo-4,4,4-trifluorobutanoate (363-57-5)

Conditions	Yield
With bromine In tetrachloromethane for 5h; Heating;	92%
With bromine In tetrachloromethane at 20℃; Reflux; Inert atmosphere;
With bromine In tetrachloromethane at 20℃; Inert atmosphere; Reflux;

ethyl 4,4,4-trifluorocrotonate (25597-16-4) → 1-trifluoromethylprop-1-en-3-ol (83706-94-9)

Conditions	Yield
With lithium aluminium tetrahydride; aluminium trichloride In diethyl ether	90%
With lithium aluminium tetrahydride; aluminium trichloride In diethyl ether at 0℃; for 2h; Hydrogenolysis;	90%
With diisobutylaluminium hydride In tert-butyl methyl ether; toluene at -70 - 25℃; for 1h; Inert atmosphere;	90%

4-butanolide (96-48-0) + ethyl 4,4,4-trifluorocrotonate (25597-16-4) → Ethyl 3-butan-4'-olid-2'-yl-3-(trifluoromethyl)propionate

Conditions	Yield
With lithium diisopropyl amide In tetrahydrofuran; hexane 1.) -78 deg C, 30 min, 2.) -78 deg C, 3.0 h;	90%

ethyl 4,4,4-trifluorocrotonate (25597-16-4) + dimethyl methane phosphonate (756-79-6) → (E)-Dimethyl 2-oxo-5,5,5-trifluoro-3-pentenylphosphonate

Conditions	Yield
With lithium diisopropyl amide In tetrahydrofuran; hexane 1.) -78 deg C, 30 min, 2.) -78 deg C, 2.0 h;	90%

2-hydroxy-3-iodo-5-(trifluoromethoxy) benzaldehyde (775330-11-5) + ethyl 4,4,4-trifluorocrotonate (25597-16-4) → ethyl 8-iodo-6-(trifluoromethoxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylate (775330-12-6)

Conditions	Yield
With triethylamine at 85℃; for 66h;	90%
With triethylamine In N,N-dimethyl-formamide at 85℃; for 66h;	90%
With triethylamine In N,N-dimethyl-formamide at 85℃; for 48h;	69%
With triethylamine In N,N-dimethyl-formamide at 85℃; for 48h;	69%
With triethylamine In N,N-dimethyl-formamide at 85℃; for 48h;	69%

5-(benzyloxy)-4-bromo-2-hydroxybenzaldehyde (775335-97-2) + ethyl 4,4,4-trifluorocrotonate (25597-16-4) → ethyl 6-(benzyloxy)-7-bromo-2-(trifluoromethyl)-2H-chromene-3-carboxylate

Conditions	Yield
With potassium carbonate In DMF (N,N-dimethyl-formamide) at 65℃; for 4h;	89%

3-bromofurane (22037-28-1) + ethyl 4,4,4-trifluorocrotonate (25597-16-4) → C10H10BrF3O3 (1353275-81-6)

Conditions	Yield
With Cl4SnC2HNOBC6H5CH(CH3)2(C6H5)2CH2C10H7 In dichloromethane at -78℃; for 8h; Diels-Alder reaction; Inert atmosphere; optical yield given as %ee; stereoselective reaction;	89%

ethyl 4,4,4-trifluorocrotonate (25597-16-4) + N-isopropyl oxazolidinone (77877-19-1) → (3R,4R,4'S)-Ethyl 3-(trifluoromethyl)-4-methyl-5-<4'-(1''-methylethyl)-2'-oxazolidinon-3'-yl>-5-oxopentanoate (138809-19-5)

Conditions	Yield
With lithium diisopropyl amide In tetrahydrofuran at -78℃; Product distribution; multistep reaction; diastereoselectivity; other acyl oxazolidinones;	88%
With lithium diisopropyl amide In tetrahydrofuran; hexane 1.) -78 deg C, 30 min, 2.) -78 deg C;	88%
With lithium diisopropyl amide 1) THF, -78 deg C, 2) -78 deg C, 1.5 h; Yield given. Multistep reaction;

ethyl 4,4,4-trifluorocrotonate (25597-16-4) + methylhydrazine (60-34-4) → 1-methyl-5-(trifluoromethyl)-2,3,4,5-tetrahydropyrazol-3-one (153893-99-3)

Conditions	Yield
at 20℃;	88%

Upstream product

• 372-30-5 ethyl 3-hydroxy-4,4,4-trifluorobutyrate 
• 64-17-5 ethanol 
• 406-94-0 4,4,4-trifluorobut-2-enoic acid 
• 372-31-6 ethyl 4,4,4-trifluoroacetoacetate 
• 887144-94-7 Togni's reagent II 
• 2459-05-4 (E)-4-ethoxy-4-oxobut-2-enoic acid 
• 79424-03-6 ethyl 4,4,4-trifluoro-2-butynate 
• 661-54-1 3,3,3-trifluoroprop-1-yne 
• 201230-82-2 carbon monoxide 
• 75-63-8 Bromotrifluoromethane 
• 140-88-5 ethyl acrylate 
• 75-90-1 2,2,2-Trifluoroacetaldehyde 
• 1099-45-2 ethyl (triphenylphosphoranylidene)acetate 
• 1522-43-6 ethyl 3-oxo-4,4,4-trifluorobutanoate enol 

Downstream Products

• 328-62-1 4,4,4-trifluoro-3-(nitromethyl)butyric acid ethyl ester 
• 590-76-1 (E)-4,4,4-trifluorocrotonamide 
• 453-32-7 3-Amino-4,4,4-trifluorbutyramid 
• 371-26-6 ethyl 4,4,4-trifluorobutanoate 
• 138852-01-4 Ethyl 3-(trifluoromethyl)-5-oxo-5-phenylvalerate 
• 138690-13-8 (3R*,4R*)-Ethyl 3-(trifluoromethyl)-4-methyl-5-oxo-5-phenylpentanoate 
• 152188-51-7 ethyl (+/-)-(3R,4R)-1-benzyl-4-(trifluoromethyl)pyrrolidine-3-carboxylate 
• 56210-75-4 ethyl (2Z)-3-trifluoromethyl-3-phenylprop-2-enoate 
• 319905-69-6 ethyl 2-phenyl-4-(trifluoromethyl)-1H-pyrrole-3-carboxylate 

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