372-31-6

Basic information

• Product Name: Ethyl 4,4,4-trifluoroacetoacetate
• Synonyms: ETHYL 3-OXO-4,4,4-TRIFLUOROACETOACETATE;ETHYL 3-OXO,4,4,4-TRIFLUOROBUTYRATE;ETHYL 4,4,4-TRIFLUOROACETOACETATE;ETHYL 4,4,4-TRIFLUOROACETOACTATE;ETHYL 4,4,4-TRIFLUORO-3-OXOBUTANOATE;ETHYL TRIFLUOROACETOACETATE;4,4,4-TRIFLUORO-3-OXOBUTANOIC ACID ETHYL ESTER;4,4,4-TRIFLUOROACETOACETIC ACID ETHYL ESTER
• CAS NO: 372-31-6
• Molecular Formula: C₆H₇F₃O₃
• Molecular Weight: 184.11
• EINECS: 206-750-7
• Product Categories: Pharmaceutical Intermediates;Aliphatics;Esters;Organic Fluorides;Fluorochemicals;Fluorinated Building Blocks;Fluorinating Reagents & Building Blocks for Fluorinated Biochemical Compounds;Synthetic Organic Chemistry
• Mol File: 372-31-6.mol

Chemical Properties

• Melting Point: -39 °C
• Boiling Point: 129-130 °C(lit.)
• Flash Point: 84 °F
• Appearance: Clear colorless to slightly yellow/Liquid
• Density: 1.259 g/mL at 25 °C(lit.)
• Vapor Pressure: 8hPa at 20℃
• Refractive Index: n20/D 1.375(lit.)
• Storage Temp.: Flammables area
• Solubility: 10g/l
• PKA: 7.76±0.10(Predicted)
• Water Solubility: 10 g/L (20 ºC)
• BRN: 608353
• CAS DataBase Reference: Ethyl 4,4,4-trifluoroacetoacetate(CAS DataBase Reference)
• NIST Chemistry Reference: Ethyl 4,4,4-trifluoroacetoacetate(372-31-6)
• EPA Substance Registry System: Ethyl 4,4,4-trifluoroacetoacetate(372-31-6)

Safety Data

• Hazard Codes: Xn,F,C,Xi
• Statements: 10-22-52/53
• Safety Statements: 61-16
• RIDADR: UN 3272 3/PG 3
• WGK Germany: 2
• TSCA: T
• HazardClass: 3
• PackingGroup: III
• Hazardous Substances Data: 372-31-6(Hazardous Substances Data)

Usage

Chemical Properties

Clear liquid

Uses

Different sources of media describe the Uses of 372-31-6 differently. You can refer to the following data:
1. Intermediate for agro chemicals and pharmaceuticals (mefloquine). Product Data Sheet
2. Widely used in the synthetic process of medicine, pesticides and organic intermediate.
3. Ethyl 4,4,4-trifluoroacetoacetate is used in the synthesis of fluorinated 2-thiouracil analogs as antithyroid agents.

Flammability and Explosibility

Flammable

InChI:InChI=1/C6H7F3O3/c1-2-12-5(11)3-4(10)6(7,8)9/h2-3H2,1H3

Synthetic route

ethyl trifluoroacetate, (383-63-1) + ethyl acetate (141-78-6) → ethyl 4,4,4-trifluoroacetoacetate (372-31-6)

Conditions	Yield
With sodium hydride In diethyl ether; paraffin reflux, 2 h and r.t., 12 h;	85%
Stage #1: ethyl acetate With sodium ethanolate at 0 - 5℃; for 1h; Stage #2: ethyl trifluoroacetate, at 0 - 65℃; for 25h;	70.7%
With diethyl ether; sodium ethanolate

diethoxyphosphoryl-acetic acid ethyl ester (867-13-0) + trimethylsilyl trifluoroacetate (400-53-3) → ethyl 4,4,4-trifluoroacetoacetate (372-31-6)

Conditions	Yield
Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With n-butyllithium In tetrahydrofuran Stage #2: trimethylsilyl trifluoroacetate In tetrahydrofuran Stage #3: With hydrogenchloride In tetrahydrofuran Further stages.;	55%
With n-butyllithium 1.) THF, -78 deg C, 20 min, 2.) THF, RT, 5 h; Yield given. Multistep reaction;

ethyl 2-fluoroacetate (459-72-3) + ethyl difluoroacetate (454-31-9) → ethyl 4,4,4-trifluoroacetoacetate (372-31-6)

Conditions	Yield
With sodium hydride

Trifluoracetyl-glyoxylsaeure-aethylester-α-hydrazon (652-71-1) → ethyl 4,4,4-trifluoroacetoacetate (372-31-6)

Conditions	Yield
With quinoline In ethanol

3-acetoxy-4,4,4-trifluoro-but-2-enoic acid ethyl ester (2707-65-5) → ethyl 4,4,4-trifluoroacetoacetate (372-31-6)

Conditions	Yield
With sodium tetrahydroborate In ethanol

ethyl trifluoroacetate, (383-63-1) + ethyl acetate (141-78-6) → Aethyl-γ,γ,γ-trifluoracetoacetat-hydrat (197850-97-8) + ethyl 4,4,4-trifluoroacetoacetate (372-31-6)

Conditions	Yield
With ethanol; sulfuric acid; sodium at 90℃; for 48h; Heating;
With sodium ethanolate In ethanol for 48h; Heating;

3-tert-Butylperoxy-4,4,4-trifluoro-3-hydroxy-butyric acid ethyl ester (129657-54-1) → tert.-butylhydroperoxide (75-91-2) + ethyl 4,4,4-trifluoroacetoacetate (372-31-6)

Conditions	Yield
In tetrachloromethane at 20℃; Equilibrium constant; Rate constant;

ethanol (64-17-5) + 2,2-Dimethyl-5-(2,2,2-trifluoro-1-hydroxy-ethylidene)-[1,3]dioxane-4,6-dione (693817-83-3) → ethyl 4,4,4-trifluoroacetoacetate (372-31-6)

Conditions	Yield
at 70℃; for 6h; Ring cleavage; Decarboxylation;

ethyl acetate (141-78-6) + sodium compound of orthotrifluoroacetic acid diethyl ester → ethyl 4,4,4-trifluoroacetoacetate (372-31-6)

diethyl ether (60-29-7) + ethyl trifluoroacetate, (383-63-1) + sodium → ethyl 4,4,4-trifluoroacetoacetate (372-31-6)

Aethyl-γ,γ,γ-trifluoracetoacetat-hydrat (197850-97-8) → ethyl 3-trifluoromethyl-3-oxo-propionate (106260-08-6) + ethyl 4,4,4-trifluoroacetoacetate (372-31-6)

Conditions	Yield
In tetrahydrofuran-d8 Equilibrium constant;

ethyl 3-trifluoromethyl-3-oxo-propionate (106260-08-6) → Aethyl-γ,γ,γ-trifluoracetoacetat-hydrat (197850-97-8) + ethyl 4,4,4-trifluoroacetoacetate (372-31-6)

Conditions	Yield
With water In tetrahydrofuran-d8 Equilibrium constant;

diazoacetic acid ethyl ester (623-73-4) + Trifluoroacetaldehyde ethyl hemiacetal (433-27-2) → ethyl 4,4,4-trifluoroacetoacetate (372-31-6)

Conditions	Yield
Stage #1: ethyl trifluoroacetaldehyde hemiacetal With sulfuric acid at 70 - 150℃; for 0.133333h; microwave irradiation; Stage #2: diazoacetic acid ethyl ester In dichloromethane at 20℃; for 0.25h; Further stages.;	15 % Chromat.

ethyl 2-diazo-3-oxo-4,4,4-trifluorobutyrate (18955-75-4) → ethyl 4,4,4-trifluoroacetoacetate (372-31-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: diisopropyl ether 2: H2O; methanol / Heating 3: quinoline / ethanol View Scheme

Trifluoracetyl-glyoxylsaeure-aethylester-triphenylphosphazin-(2) (2559-41-3) → ethyl 4,4,4-trifluoroacetoacetate (372-31-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: H2O; methanol / Heating 2: quinoline / ethanol View Scheme

sodium 4-ethoxy-1,1,1-trifluoro-4-oxobut-2-en-2-olate (22466-45-1) → ethyl 4,4,4-trifluoroacetoacetate (372-31-6)

Conditions	Yield
With hydrogenchloride In water at 5 - 10℃; for 3h; pH=1 - 3;

1,1,1-trifluoro-2-propanone (421-50-1) + Diethyl carbonate (105-58-8) → ethyl 4,4,4-trifluoroacetoacetate (372-31-6)

Conditions	Yield
With sodium hydride In toluene Inert atmosphere; Reflux;

biguanide sulfate (2583-53-1, 6945-23-9, 49719-55-3) + ethyl 4,4,4-trifluoroacetoacetate (372-31-6) → N-(4-hydroxy-6-trifluoromethyl-pyrimidin-2-yl)-guanidine

Conditions	Yield
Stage #1: biguanide sulfate With sodium hydroxide In ethanol at 0 - 20℃; Stage #2: ethyl 4,4,4-trifluoroacetoacetate In ethanol for 2.5h; Heating; Further stages.;	100%

ethyl 4,4,4-trifluoroacetoacetate (372-31-6) + benzyl alcohol (100-51-6) → benzyl 4,4,4-trifluoroacetoacetate (83097-87-4)

Conditions	Yield
In toluene at 120℃; for 5h; Dean-Stark;	100%
In toluene Heating;

ethyl 4,4,4-trifluoroacetoacetate (372-31-6) + 4-(2-hydroxy-benzylidene)-5-methyl-2-phenyl-2,4-dihydro-pyrazol-3-one (68761-48-8) → 5-ethoxylcarbonyl-6-hydroxy-4-(2-hydroxyphenyl)-1-phenyl-3-methyl-6-(trifluoromethyl)-1,4,5,6-tetrahydropyrazolo[3,4-b]pyran

Conditions	Yield
With ammonium acetate In ethanol at 20℃; for 2h;	100%

aluminum ethoxide (555-75-9) + ethyl 4,4,4-trifluoroacetoacetate (372-31-6) + acetylacetone (123-54-6) → monoacetylacetonate aluminum bis(ethyl-4,4,4-trifluoroacetoacetate)

Conditions	Yield
In toluene at 20℃; for 24h;	100%

ethyl 4,4,4-trifluoroacetoacetate (372-31-6) → ethyl 2-chloro-4,4,4-trifluoro-3-oxobutanoate (363-58-6)

Conditions	Yield
With sulfuryl dichloride In dichloromethane at -5 - 20℃;	99.3%
With chlorine In acetone	95%
With chlorine at 0 - 30℃; Cooling with acetone-dry ice;	95%

ethyl 4,4,4-trifluoroacetoacetate (372-31-6) + recorcinol (108-46-3) → 7-hydroxy-4-(trifluoromethyl)-2H-chromen-2-one (575-03-1)

Conditions	Yield
With iodine In toluene at 80℃; Pechmann reaction;	99%
With magnesium bis(trifluoromethane solfonyl)imide In neat (no solvent) at 80℃; for 0.416667h; Pechmann Condensation;	97%
indium(III) chloride at 65℃; for 0.5h; von Pechmann reaction;	96%

ethyl 4,4,4-trifluoroacetoacetate (372-31-6) → ethyl 3-hydroxy-4,4,4-trifluorobutyrate (372-30-5)

Conditions	Yield
With formic acid; C18H24ClIrN3 In water at 80℃; for 8h; Schlenk technique; Inert atmosphere; chemoselective reaction;	99%
With sodium tetrahydroborate In diethyl ether 1.) 0-5 deg C, 1 h, 2.) r.t., overnight;	98%
With sodium tetrahydroborate In diethyl ether	97%

7-ethyl-1H-indole (22867-74-9) + ethyl 4,4,4-trifluoroacetoacetate (372-31-6) → ethyl 3-(7-ethyl-1H-indol-3-yl)-4,4,4-trifluoro-3-hydroxybutanoate

Conditions	Yield
With (S)-3,3'-bis(2,4,6-tri-iso-propylphenyl)-1,1'-binaphthyl-2,2'-diyl hydrogenphosphate In dichloromethane at 20℃; for 76h; Friedel-Crafts reaction; optical yield given as %ee; enantioselective reaction;	99%

4-chlorobenzylamine (104-86-9) + ethyl 4,4,4-trifluoroacetoacetate (372-31-6) → ethyl 3-(4-chlorobenzyl)amino-4,4,4-trifluorobut-2-enoate (1384849-55-1)

Conditions	Yield
Stage #1: 4-chlorobenzylamine With acetic acid In chloroform at 20℃; for 0.0833333h; Stage #2: ethyl 4,4,4-trifluoroacetoacetate In chloroform for 5h; Reflux;	99%

6-methylbenzothiazol-2-ylamine (2536-91-6) + ethyl 4,4,4-trifluoroacetoacetate (372-31-6) → 8-methyl-2-(trifluoromethyl)-4H-benzo[4,5]thiazolo[3,2-a]pyrimidin-4-one

Conditions	Yield
With indium(III) triflate In toluene at 100℃; for 16h; regioselective reaction;	99%

4-hydrazinobenzene-1-sulfonamide hydrochloride (17852-52-7, 27918-19-0) + ethyl 4,4,4-trifluoroacetoacetate (372-31-6) → 4-(5-hydroxy-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide (627094-59-1)

Conditions	Yield
In ethanol at 24℃; Reflux; Inert atmosphere;	99%

1,3-cylohexanedione (504-02-9) + ethyl 4,4,4-trifluoroacetoacetate (372-31-6) → 4-(trifluoromethyl)-7,8-dihydro-2H-chromene-2,5(6H)-dione

Conditions	Yield
With 2-(Dimethylamino)pyridine In 1,2-dichloro-ethane at 120℃; for 16h; Catalytic behavior; Reagent/catalyst; Solvent; Temperature; Pechmann Condensation; Glovebox; Inert atmosphere;	99%

5-methylcyclohexan-1,3-dione (4341-24-6) + ethyl 4,4,4-trifluoroacetoacetate (372-31-6) → 7-methyl-4-(trifluoromethyl)-7,8-dihydro-2H-chromene-2,5(6H)-dione

Conditions	Yield
With 2-(Dimethylamino)pyridine In 1,2-dichloro-ethane at 120℃; for 16h; Pechmann Condensation; Glovebox; Inert atmosphere;	99%

dimedone (126-81-8) + ethyl 4,4,4-trifluoroacetoacetate (372-31-6) → 7,7-dimethyl-4-(trifluoromethyl)-7,8-dihydro-2H-chromene-2,5(6H)-dione

Conditions	Yield
With 2-(Dimethylamino)pyridine In 1,2-dichloro-ethane at 120℃; for 16h; Pechmann Condensation; Glovebox; Inert atmosphere;	99%

5-phenyl-cyclohexane-1,3-dione (493-72-1) + ethyl 4,4,4-trifluoroacetoacetate (372-31-6) → 7-phenyl-4-(trifluoromethyl)-7,8-dihydro-2H-chromene-2,5(6H)-dione

Conditions	Yield
With 2-(Dimethylamino)pyridine In 1,2-dichloro-ethane at 120℃; for 16h; Pechmann Condensation; Glovebox; Inert atmosphere;	99%

ethyl 4,4,4-trifluoroacetoacetate (372-31-6) + 4-aminosulfonylphenylhydrazine (4392-54-5) → 4-(5-hydroxy-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide (627094-59-1)

Conditions	Yield
In ethanol for 12h; Reflux;	99%

orthoformic acid triethyl ester (122-51-0) + ethyl 4,4,4-trifluoroacetoacetate (372-31-6) → ethyl 2-(ethoxymethylidene)-4,4,4-trifluoro-3-oxobutanoate (571-55-1)

Conditions	Yield
With acetic anhydride at 120 - 140℃; for 7h; Condensation;	98%
With acetic anhydride at 135℃; for 18h;	97.1%
In acetic anhydride for 8h; Reflux;	95%

ethyl 4,4,4-trifluoroacetoacetate (372-31-6) → 5-(trifluoromethyl)-4-pyrazolin-3-one (76480-99-4)

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

5-amino-1,2-dihydropyrazol-3-one (28491-52-3) + ethyl 4,4,4-trifluoroacetoacetate (372-31-6) → 4-trifluoromethyl-6-hydroxy-3-oxo-2,3-dihydropyrazolo<3,4-b>pyridine

Conditions	Yield
With acetic acid for 2h; Heating;	98%

ethyl 4,4,4-trifluoroacetoacetate (372-31-6) + m-Hydroxyaniline (591-27-5) → Coumarin 151 (53518-15-3)

Conditions	Yield
With magnesium bis(trifluoromethane solfonyl)imide In neat (no solvent) at 80℃; for 0.416667h; Pechmann Condensation;	98%
With sulfuric acid In ethanol at 80℃;	83%
With zinc(II) chloride In ethanol for 12h; Heating;	69%
With zinc(II) chloride In ethanol Reflux;	12%
With zinc(II) chloride In ethanol for 12h; Reflux;

ethyl 4,4,4-trifluoroacetoacetate (372-31-6) → ethyl 3-amino-4,4,4-trifluorocrotonate (141860-78-8)

Conditions	Yield
With ammonium acetate In cyclohexane; isopropyl alcohol	98%
With ammonium acetate In ethanol; water	88%
With ammonia

2,3;4,5-di-O-isopropylidene-β-D-fructopyranose (20880-92-6) + ethyl 4,4,4-trifluoroacetoacetate (372-31-6) → 4,4,4-Trifluoro-3-oxo-butyric acid (3aS,5aR,8aR,8bS)-2,2,7,7-tetramethyl-tetrahydro-bis[1,3]dioxolo[4,5-b;4',5'-d]pyran-3a-ylmethyl ester

Conditions	Yield
With vermiculite In toluene for 48h; Heating;	98%

((3aR,4R,6R,6aR)-6-methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol (4099-85-8) + ethyl 4,4,4-trifluoroacetoacetate (372-31-6) → 4,4,4-Trifluoro-3-oxo-butyric acid (3aR,4R,6R,6aR)-6-methoxy-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethyl ester

Conditions	Yield
With vermiculite In toluene for 48h; Heating;	98%

indole (120-72-9) + ethyl 4,4,4-trifluoroacetoacetate (372-31-6) → 3-hydroxy-3-(indol-3-yl)-4,4,4-trifluorobutanoic acid ethyl ester

Conditions	Yield
With K-10 montmorillonite In toluene at 70℃; for 1h; Friedel-Crafts hydroxyalkylation;	98%

2-methyl-1H-indole (95-20-5) + ethyl 4,4,4-trifluoroacetoacetate (372-31-6) → 3-hydroxy-3-(2-methylindol-3-yl)-4,4,4-trifluorobutanoic acid ethyl ester

Conditions	Yield
With K-10 montmorillonite In toluene at 70℃; for 0.75h; Friedel-Crafts hydroxyalkylation;	98%

pyrrole (109-97-7) + ethyl 4,4,4-trifluoroacetoacetate (372-31-6) → 3-hydroxy-3-(pyrrol-2-yl)-4,4,4-trifluorobutanoic acid ethyl ester

Conditions	Yield
With K-10 montmorillonite In toluene at 70℃; for 0.5h; Friedel-Crafts hydroxyalkylation;	98%

phenylhydrazine (100-63-0) + ethyl 4,4,4-trifluoroacetoacetate (372-31-6) → 1-phenyl-3-(trifluoromethyl)-1H-pyrazol-5(4H)-one (321-07-3)

Conditions	Yield
at 150 - 160℃; for 3h;	98%
With acetic acid for 6h; Reflux;	90%
With acetic acid Reflux;	90%

ethyl 4,4,4-trifluoroacetoacetate (372-31-6) → ethyl (3R)-4,4,4-trifluoro-3-hydroxybutanoate (85571-85-3)

Conditions	Yield
With α-D-glucose 6-phosphate; permeabilized cells of Bacillus pumilus Phe-C3; NADPH In various solvent(s) at 25℃; for 24h; pH=7.0;	98%
With glucose dehydrogenase; pET28-bmgdh-cgcr; sodium carbonate In aq. phosphate buffer; toluene at 30℃; for 12h; pH=6.5; Enzymatic reaction; enantioselective reaction;	92%
With nicotinamide adenine dinucleotide phosphate; isopropyl alcohol In dimethyl sulfoxide at 30℃; for 24h; pH=7.5; Reagent/catalyst; Enzymatic reaction; enantioselective reaction;	66%

phenylhydrazine (100-63-0) + ethyl 4,4,4-trifluoroacetoacetate (372-31-6) → 1-phenyl-3-trifluoromethyl-5-hydroxypyrazole (96145-98-1)

Conditions	Yield
With acetic acid at 10 - 80℃; for 6.5h;	98%
In ethanol at 24℃; for 12h; Reflux; Inert atmosphere;	92%
In ethanol for 12h; Reflux;	92%

ethyl 4,4,4-trifluoroacetoacetate (372-31-6) + methylamine (74-89-5) → 3-methylamino-4,4,4-trifluorobut-2-enoic acid ethyl ester (507448-65-9)

Conditions	Yield
With acetic acid In ethanol; methyl cyclohexane at 80 - 90℃; under 760.051 Torr; for 3 - 4h; Product distribution / selectivity;	98%
With acetic acid In methyl cyclohexane at 80 - 85℃; for 3 - 8h; Product distribution / selectivity;	88.5%

Upstream product

• 459-72-3 ethyl 2-fluoroacetate 
• 454-31-9 ethyl difluoroacetate 
• 383-63-1 ethyl trifluoroacetate, 
• 141-78-6 ethyl acetate 
• 652-71-1 Trifluoracetyl-glyoxylsaeure-aethylester-α-hydrazon 
• 2707-65-5 3-acetoxy-4,4,4-trifluoro-but-2-enoic acid ethyl ester 
• 129657-54-1 3-tert-Butylperoxy-4,4,4-trifluoro-3-hydroxy-butyric acid ethyl ester 
• 867-13-0 diethoxyphosphoryl-acetic acid ethyl ester 
• 400-53-3 trimethylsilyl trifluoroacetate 
• 64-17-5 ethanol 
• 693817-83-3 2,2-Dimethyl-5-(2,2,2-trifluoro-1-hydroxy-ethylidene)-[1,3]dioxane-4,6-dione 
• 60-29-7 diethyl ether 
• 197850-97-8 Aethyl-γ,γ,γ-trifluoracetoacetat-hydrat 
• 106260-08-6 ethyl 3-trifluoromethyl-3-oxo-propionate 

Downstream Products

• 723-74-0 1-methyl-2-phenyl-5-trifluoromethyl-1,2-dihydro-3H-pyrazol-3-one 
• 368-54-7 2-sulfanylidene-6-(trifluoromethyl)-2,3-dihydropyrimidin-4(1H)-one 
• 2924-80-3 ethyl (Z)-4,4,4-trifluoro-3-oxo-2-(ureidomethylidene)butanoate 
• 571-55-1 ethyl 2-(ethoxymethylidene)-4,4,4-trifluoro-3-oxobutanoate 
• 782-55-8 2-(trifluoroacetonyl)benzimidazole 
• 781-93-1 3-trifluoromethyl-1-phenyl-1H-pyrazol-5(4H)-one 
• 2836-44-4 2-methyl-4-(trifluoromethyl)-1H-pyrimidin-6-one 
• 73981-89-2 ethyl (2Z)-4,4,4-trifluoro-3-oxo-2-(2-phenylhydrazinylidene)butanoate 
• 672-45-7 6-trifluoromethyluracil 
• 575-03-1 7-hydroxy-4-(trifluoromethyl)-2H-chromen-2-one 
• 76480-99-4 5-(trifluoromethyl)-4-pyrazolin-3-one 
• 421-50-1 1,1,1-trifluoro-2-propanone 
• 400-36-2 trifluoroacetylacetic acid 
• 363-58-6 ethyl 2-chloro-4,4,4-trifluoro-3-oxobutanoate 

Relevant articles and documents

Synthetic method of ethyl 4,4,4-trifluoroacetoacetate

The invention relates to a synthetic method of ethyl 4,4,4-trifluoroacetoacetate, belonging to the field of chemical synthesis. According to the invention, trifluoroacetone and ethyl chloroformate are used as raw materials, hydrogen chloride is used as a catalyst, and a reaction is carried out in a pipeline reactor. The invention provides the novel method for synthesizing the ethyl 4,4,4-trifluoroacetoacetate; and the ethyl chloroformate with higher reaction activity is adopted and the reaction is catalyzed by hydrogen chloride, so reaction time is shortened, the self-condensation reaction of the ethyl 4,4,4-trifluoroacetoacetate in strong acid and strong alkali systems is avoided, and reaction yield and product purity are improved.

Preparation method of sodium formate

The invention discloses a preparation method of sodium formate. The method adopts trifluoroacetoacetic acid ethyl enol sodium salt and formic acid as raw materials, and comprises the following steps: A1, adding formic acid into an ethyl trifluoroacetoacetate enol sodium salt solution, controlling the temperature at 10-60 DEG C, and carrying out heat preservation reaction for 2.0-5.0 hours after the formic acid is added; and A2, carrying out solid-liquid separation on the reaction liquid, wherein the separated solid is crude sodium formate. The method has the advantages of mild reaction, high safety, high sodium formate purity, basically no three wastes and the like.

Cu-Mediated Expeditious Annulation of Alkyl 3-Aminoacrylates with Aryldiazonium Salts: Access to Alkyl N2-Aryl 1,2,3-Triazole-carboxylates for Druglike Molecular Synthesis

Alkyl N-aryl 1,2,3-triazole-carboxylates are important molecules or intermediates in medicinal chemistry, but the synthesis of N2-aryl counterparts remains elusive. Herein, we describe a Cu-mediated annulation reaction of alkyl 3-aminoacrylates with aryldiazonium salts, both of which are readily available substrates. Furthermore, alkyl 2-aminoacrylates are also viable substrates. Diverse alkyl N2-aryl 1,2,3-triazole-carboxylates and their analogues can be rapidly prepared under mild conditions. Especially, this protocol allows one to access several druglike variants of carbonic anhydrase inhibitors and celecoxib.

Production technology of ethyl trifluoroacetoacetate

Ethyl trifluoroacetoacetate is an important chemical engineering raw material. The process flow of a production technology of ethyl trifluoroacetoacetate comprises the following steps: 1, a condensation reaction; 2, first-stage distillation; 3, neutralization; 4, suction filtration; 5, rectification; 6, esterification recovery; and 7, second-stage distillation.

Preparation of fluorine-containing methyl or aryl alkyl ketone method

The invention discloses a method for preparing fluorine-containing methyl or alkylaryl ketones, belonging to an organic synthesis field. The method comprises two steps of: ester condensation: ester condensation reaction of an R1COOR2 compound represented by a formula A with a R2COOR2 compound represented by a formula B, is performed to form an R1COCH(R3)COOR2 intermediate represented by a formula C; and ester interchange: R1COCH(R3)COOR2 represented by the formula C is carried out ester interchange reaction with R2COOH under 100-110 DEG C and with catalysis of dilute H2SO4 or a cationic resin, and then decarboxylating to obtain R1COR2 fluorine-containing methyl or alkylaryl ketones represented by a formula D. The R1 group may be CF3-, CF2-, CF- or Ar-; the R2 group may be CH3-, Et- and n-Pr; and the R3 group may be CH3-, Et- and H-. Ester interchange in the invention avoids formation of HOR2 which has a nearly same boiling point with the compound represented by the formula D and is azeotropic with the compound represented by the formula D, enables the compound represented by the formula D to be purified without series rectification operation, and is suitable for large scale production. Simultaneously, ester interchange in the invention greatly raises cost. An ion exchange resin completes ester interchange in a waterless condition, which avoids a de-watering step, and simplifies technologies.

Synthesis method of 6-trifluoromethyl-N-(2-trifluoromethylindole-5-yl)methyl-4-pyrimidinamine

The invention discloses a synthesis method of 6-trifluoromethyl-N-(2-trifluoromethylindole-5-yl)methyl-4-pyrimidinamine, relates to a chemical synthesis method, and especially relates to a novel synthesis method of 6-trifluoromethyl-N-(2-trifluoromethylindole-5-yl)methyl-4-pyrimidinamine. According to the synthesis method, 6-trifluoromethyl-N-(2-trifluoromethylindole-5-yl)methyl-4-pyrimidinamine is obtained through Claisen condensation, cyclization, chlorination, and hydrocarbonylation reactions. Compared with the conventional methods, the cyclization is improved, materials can be continuously fed in chlorination and hydrocarbonylation steps, one-pot operation is realized, and the method is suitable for industrial production.

PROCESS FOR PREPARING ALKYL 3-DIFLUOROMETHYL-1-METHYL-1H-PYRAZOLE-4-CARBOXYLATE AND ITS ANALOGS

The disclosure provides a process for the preparation of alkyl 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylate and its analogs. The process includes a reaction workup method for Claisen condensation, wherein the enolate salt is acidified after removing remaining starting material and byproducts such as, ethanol and excessive ethyl acetate. The process also includes a method for completely drying alkyl difluoroacetoacetate and its analogs before use in the next step by reacting trialkyl orthoformate with the residual water. The process includes using Na2CO3 and /or K2CO3 to promote the ring-closure reaction to produce the alkyl 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylate. The process also includes effectively removing the regioisomer, alkyl 3-difluoromethyl-2-methyl-1H-pyrazole-4-caboxylate formed as a byproduct of the ring closure by a precipitation in a mixed solvent system and thereby eliminating the need for recrystallization of the final product.

A PROCESS FOR THE PREPARATION OF ALKYL 3-DIFLUOROMETHYL-1-METHYL-1H-PYRAZOLE-4-CARBOXYLATE AND ITS ANALOGS

The disclosure provides a process for the preparation of alkyl 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylate and its analogs. The process includes a reaction workup method for Claisen condensation, wherein the enolate salt is acidified after removing remaining starting material and byproducts such as, ethanol and excessive ethyl acetate. The process also includes a method for completely drying alkyl difluoroacetoacetate and its analogs before use in the next step by reacting trialkyl orthoformate with the residual water. The process includes using Na2CO3 and/or K2CO3 to promote the ring-closure reaction to produce the alkyl 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylate. The process also includes effectively removing the regioisomer, alkyl 3-difluoromethyl-2-methyl-1H-pyrazole-4-carboxylate formed as a byproduct of the ring closure by a precipitation in a mixed solvent system and thereby eliminating the need for recrystallization of the final product.

Tetrafluorine-containing ketones and acetoacetates: Synthesis and mechanistic study

Addition of trimethylsilyl trifluoroacetate to the carbanions of α-fluorobenzyl-phosphonate (3) or diisopropyl(fluorocarbethoxymethyl) phosphonate (9) formed the corresponding intermediates [CF3C(O)CFPh] -Li+ (10) and [CF3C(O)CFCO2Et] -Li+ (11), respectively. Subsequent protonation, alkylation or allylation of 10 and 11 afforded trifluoromethyl fluorobenzyl ketones 12 and ethyl 2,4,4,4-tetra-fluoroacetoacetates 13. Based on the results obtained, a plausible mechanism was proposed.

Microwave-assisted preparation of trifluoroacetaldehyde (fluoral): isolation and applications

A novel method for the preparation of trifluoroacetaldehyde (fluoral, TFAc, CF3CHO) from commercially available trifluoroacetaldehyde ethylhemiacetal (TFAE) by microwave irradiation is described. The isolation, characterization and reaction of fluoral with various nucleophiles were studied to verify the diverse applicability of this new method.