101987-86-4

Basic information

• Product Name: ETHYL 3-(3-CHLORO-2,4,5-TRIFLUOROPHENYL)-3-OXOPROPANOATE
• Synonyms: ETHYL 3-(3-CHLORO-2,4,5-TRIFLUOROPHENYL)-3-OXOPROPANOATE;Ethyl 2-(3-chloro-2,4,5-trifluorobenzoyl)acetate;Ethyl 3-chloro-2,4,5-trifluorobenzoylacetate;Benzenepropanoic acid,3-chloro-2,4,5-trifluoro-b-oxo-, ethyl ester;"3-(3-Chloro-2,4,5-trifluoro-phenyl)-3-oxo- propionic acid ethyl ester ";ethyl beta-(3-chloro-2,4,5-trifluorophenyl)-beta-oxopropionate;3-(3-chloro-2,4,5-trifluorophenyl)-3-oxopropanoic acid
• CAS NO: 101987-86-4
• Molecular Formula: C₁₁H₈ClF₃O₃
• Molecular Weight: 280.6276296
• EINECS: 1806241-263-5
• Mol File: 101987-86-4.mol
• Article Data: 4

Chemical Properties

• Melting Point: 80-83℃
• Boiling Point: 325℃
• Flash Point: 130℃
• Appearance: /
• Density: 1.413
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.484
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 10.32±0.50(Predicted)
• CAS DataBase Reference: ETHYL 3-(3-CHLORO-2,4,5-TRIFLUOROPHENYL)-3-OXOPROPANOATE(CAS DataBase Reference)
• NIST Chemistry Reference: ETHYL 3-(3-CHLORO-2,4,5-TRIFLUOROPHENYL)-3-OXOPROPANOATE(101987-86-4)
• EPA Substance Registry System: ETHYL 3-(3-CHLORO-2,4,5-TRIFLUOROPHENYL)-3-OXOPROPANOATE(101987-86-4)

Safety Data

• Hazardous Substances Data: 101987-86-4(Hazardous Substances Data)

Usage

Chemical Properties

off-white solid

Uses

Ethyl 3-?(3-?Chloro-?2,?4,?5-?trifluorophenyl)?-?3-?oxopropanoate is a reagent used in the preparation of fluoroquinolone derivatives as antibacterial and antimycobacterial agents.

InChI:InChI=1/C11H8ClF3O3/c1-2-18-8(17)4-7(16)5-3-6(13)11(15)9(12)10(5)14/h3H,2,4H2,1H3

Synthetic route

ethyl potassium malonate (6148-64-7) + 3-Chloro-2,4,5-trifluorobenzoyl chloride (101513-78-4) → ethyl β-(3-chloro-2,4,5-trifluorophenyl)-β-oxopropionate (101987-86-4)

Conditions	Yield
With triethylamine; magnesium chloride 1.) MeCN, 20 to 25 deg C, 2.5 h, 2.) 20 to 25 deg C, 12 h; Yield given. Multistep reaction;

dipyridyl + hydrogen ethyl malonate (1071-46-1) + 3-Chloro-2,4,5-trifluorobenzoyl chloride (101513-78-4) → ethyl β-(3-chloro-2,4,5-trifluorophenyl)-β-oxopropionate (101987-86-4)

Conditions	Yield
With hydrogenchloride; n-butyllithium In tetrahydrofuran
With hydrogenchloride; n-butyllithium In tetrahydrofuran

3-Chloro-2,4,5-trifluorobenzoic acid (101513-77-3) → ethyl β-(3-chloro-2,4,5-trifluorophenyl)-β-oxopropionate (101987-86-4)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: thionyl chloride / N,N-dimethyl-formamide / 4 h / Reflux 2.1: magnesium / tetrachloromethane; ethanol / 3.25 h / Reflux 2.2: 2.33 h / -10 °C 3.1: toluene-4-sulfonic acid / water / 5 h / Reflux View Scheme

3-Chloro-2,4,5-trifluorobenzoyl chloride (101513-78-4) → ethyl β-(3-chloro-2,4,5-trifluorophenyl)-β-oxopropionate (101987-86-4)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: magnesium / tetrachloromethane; ethanol / 3.25 h / Reflux 1.2: 2.33 h / -10 °C 2.1: toluene-4-sulfonic acid / water / 5 h / Reflux View Scheme

C14H12ClF3O5 → ethyl β-(3-chloro-2,4,5-trifluorophenyl)-β-oxopropionate (101987-86-4)

Conditions	Yield
With toluene-4-sulfonic acid In water for 5h; Reflux;

(1R,2S)-2-fluorocyclopropylamine p-toluenesulfonic acid salt (143062-84-4) + ethyl β-(3-chloro-2,4,5-trifluorophenyl)-β-oxopropionate (101987-86-4) + orthoformic acid triethyl ester (122-51-0) → (Z)-ethyl 2-(3-chloro-2,4,5-trifluorobenzoyl)-3-[{(1R,2S)-2-fluorocyclopropyl}amino]acrylate

Conditions	Yield
Stage #1: ethyl β-(3-chloro-2,4,5-trifluorophenyl)-β-oxopropionate; orthoformic acid triethyl ester With acetic anhydride at 110 - 120℃; for 1.5h; Stage #2: (1R,2S)-2-fluorocyclopropylamine p-toluenesulfonic acid salt With triethylamine; trifluoroacetic acid In dichloromethane at 20℃; for 1h;	78%

ethyl β-(3-chloro-2,4,5-trifluorophenyl)-β-oxopropionate (101987-86-4) + tert-butyl (5-amino-2,4-difluorophenyl)carbamate (179741-60-7) + methyl iodide (74-88-4) → Ethyl 3-ethoxy-2-(3'-chloro-2',4',5'-trifluorobenzoyl)acrylate

Conditions	Yield
With potassium carbonate In ethanol; chloroform; water; N,N-dimethyl-formamide

3,5-diamino-2-chloropyridine (5632-81-5) + ethyl β-(3-chloro-2,4,5-trifluorophenyl)-β-oxopropionate (101987-86-4) + orthoformic acid triethyl ester (122-51-0) → ethyl 3-[(5-amino-6-chloropyridin-3-yl)amino]-2-(3-chloro-2,4,5-trifluorobenzoyl)acrylate

Conditions	Yield
With acetic anhydride In ethanol; chloroform; toluene

N-tert-butoxycarbonyl-2,4-difluoro-m-phenylenediamine (208166-48-7) + ethyl β-(3-chloro-2,4,5-trifluorophenyl)-β-oxopropionate (101987-86-4) + formic acid ethyl ester (109-94-4) → ethyl 1-(5-tert-butoxycarbonylamino-2,4-difluorophenyl)-8-chloro-6,7-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate (197520-73-3)

Conditions	Yield
With acetic anhydride; potassium carbonate In chloroform methanol; hexane; chloroform; N,N-dimethyl-formamide

Ethyl 3-ethoxy-2-(3'-chloro-2',4',5'-trifluorobenzoyl)acrylate + 2-Amino-3,5,6-trifluoropyridine (3534-50-7) + ethanolamine (141-43-5) + ethyl β-(3-chloro-2,4,5-trifluorophenyl)-β-oxopropionate (101987-86-4) → ethyl 8-Chloro-6,7-difluoro-1-[3,5-difluoro-6-(2-hydroxyethylamino)pyridin-2-yl]-4-oxo-1,4-dihydroquinoline-3-carboxylate

Conditions	Yield
With 1-methyl-pyrrolidin-2-one; potassium carbonate In ethanol; chloroform; water; N,N-dimethyl-formamide

4-fluoro-3-methoxyaniline (64465-53-8) + ethyl β-(3-chloro-2,4,5-trifluorophenyl)-β-oxopropionate (101987-86-4) → ethyl 8-chloro-6,7-difluoro-1-(4-fluoro-3-methoxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxylate (208166-16-9)

Conditions	Yield
With potassium carbonate In ethanol; chloroform; water; N,N-dimethyl-formamide

ethyl β-(3-chloro-2,4,5-trifluorophenyl)-β-oxopropionate (101987-86-4) + orthoformic acid triethyl ester (122-51-0) → ethyl 2-(3-chloro-2,4,5-trifluorobenzoyl)-3-ethoxyacrylate

Conditions	Yield
With acetic anhydride
With acetic anhydride

3-aminoisoxazole (1750-42-1) + ethyl β-(3-chloro-2,4,5-trifluorophenyl)-β-oxopropionate (101987-86-4) + orthoformic acid triethyl ester (122-51-0) + citric acid (77-92-9) → ethyl 8-chloro-6,7-difluoro-1-(isoxazol-3-yl)-1,4-dihydro-4-oxoquinoline-3-carboxylate

Conditions	Yield
With acetic anhydride; potassium carbonate In N-methyl-acetamide; hexane; chloroform

3-acetylaminopyrrolidine (79286-74-1) + ethyl β-(3-chloro-2,4,5-trifluorophenyl)-β-oxopropionate (101987-86-4) → ethyl 2-[4-(3-acetamido-1-pyrrolidinyl)-3-chloro-2,5-difluorobenzoyl]acetate

Conditions	Yield
With sodium hydrogencarbonate In acetonitrile

ethyl β-(3-chloro-2,4,5-trifluorophenyl)-β-oxopropionate (101987-86-4) → 2-(3-chloro-2,4,5-trifluorobenzoyl)-3-{[(1R,2S)-2-fluorocyclopropyl]amino}acrylate ethyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1: acetic anhydride / 8 h / Reflux 2: triethylamine / dichloromethane / 2 h / 20 °C View Scheme

ethyl β-(3-chloro-2,4,5-trifluorophenyl)-β-oxopropionate (101987-86-4) → 8-chloro-6,7-difluoro-1-[(1R,2S)-2-fluorocyclopropyl]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester (127199-25-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: acetic anhydride / 8 h / Reflux 2: triethylamine / dichloromethane / 2 h / 20 °C 3: potassium carbonate / N,N-dimethyl-formamide / 1 h / 90 °C View Scheme
Multi-step reaction with 2 steps 1.1: acetic anhydride / 1.5 h / 110 - 120 °C 1.2: 1 h / 20 °C 2.1: sodium hydride / 1,4-dioxane / 1 h View Scheme

ethyl β-(3-chloro-2,4,5-trifluorophenyl)-β-oxopropionate (101987-86-4) → C17H12BClF3NO7

Conditions	Yield
Multi-step reaction with 4 steps 1.1: acetic anhydride / 8 h / Reflux 2.1: triethylamine / dichloromethane / 2 h / 20 °C 3.1: potassium carbonate / N,N-dimethyl-formamide / 1 h / 90 °C 4.1: 1.5 h / 110 °C 4.2: 95 - 110 °C View Scheme

ethyl β-(3-chloro-2,4,5-trifluorophenyl)-β-oxopropionate (101987-86-4) → 7-[3-amino-4-(methoxyimino)piperidin-1-yl]-8-chloro-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

Conditions	Yield
Multi-step reaction with 6 steps 1.1: acetic anhydride / 8 h / Reflux 2.1: triethylamine / dichloromethane / 2 h / 20 °C 3.1: potassium carbonate / N,N-dimethyl-formamide / 1 h / 90 °C 4.1: 1.5 h / 110 °C 4.2: 95 - 110 °C 5.1: acetonitrile / 20 °C / Inert atmosphere 6.1: sodium hydroxide / 1 h / 20 °C 6.2: pH 6.5 - 7 View Scheme

ethyl β-(3-chloro-2,4,5-trifluorophenyl)-β-oxopropionate (101987-86-4) → 7-[3-(aminomethyl)-4-(methoxyimino)pyrrolidin-1-yl]-8-chloro-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

Conditions	Yield
Multi-step reaction with 6 steps 1.1: acetic anhydride / 8 h / Reflux 2.1: triethylamine / dichloromethane / 2 h / 20 °C 3.1: potassium carbonate / N,N-dimethyl-formamide / 1 h / 90 °C 4.1: 1.5 h / 110 °C 4.2: 95 - 110 °C 5.1: acetonitrile / 20 °C / Inert atmosphere 6.1: sodium hydroxide / 1 h / 20 °C 6.2: pH 6.5 - 7 View Scheme

ethyl β-(3-chloro-2,4,5-trifluorophenyl)-β-oxopropionate (101987-86-4) → 7-[3-(aminomethyl)-4-(ethoxyimino)pyrrolidin-1-yl]-8-chloro-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

Conditions	Yield
Multi-step reaction with 6 steps 1.1: acetic anhydride / 8 h / Reflux 2.1: triethylamine / dichloromethane / 2 h / 20 °C 3.1: potassium carbonate / N,N-dimethyl-formamide / 1 h / 90 °C 4.1: 1.5 h / 110 °C 4.2: 95 - 110 °C 5.1: acetonitrile / 20 °C / Inert atmosphere 6.1: sodium hydroxide / 1 h / 20 °C 6.2: pH 6.5 - 7 View Scheme

ethyl β-(3-chloro-2,4,5-trifluorophenyl)-β-oxopropionate (101987-86-4) → 7-[3-(aminomethyl)-4-(benzyloxyimino)pyrrolidin-1-yl]-8-chloro-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

Conditions	Yield
Multi-step reaction with 6 steps 1.1: acetic anhydride / 8 h / Reflux 2.1: triethylamine / dichloromethane / 2 h / 20 °C 3.1: potassium carbonate / N,N-dimethyl-formamide / 1 h / 90 °C 4.1: 1.5 h / 110 °C 4.2: 95 - 110 °C 5.1: acetonitrile / 20 °C / Inert atmosphere 6.1: sodium hydroxide / 1 h / 20 °C 6.2: pH 6.5 - 7 View Scheme

ethyl β-(3-chloro-2,4,5-trifluorophenyl)-β-oxopropionate (101987-86-4) → C23H24BClF2N4O8

Conditions	Yield
Multi-step reaction with 5 steps 1.1: acetic anhydride / 8 h / Reflux 2.1: triethylamine / dichloromethane / 2 h / 20 °C 3.1: potassium carbonate / N,N-dimethyl-formamide / 1 h / 90 °C 4.1: 1.5 h / 110 °C 4.2: 95 - 110 °C 5.1: acetonitrile / 20 °C / Inert atmosphere View Scheme

ethyl β-(3-chloro-2,4,5-trifluorophenyl)-β-oxopropionate (101987-86-4) → C23H24BClF2N4O8

Conditions	Yield
Multi-step reaction with 5 steps 1.1: acetic anhydride / 8 h / Reflux 2.1: triethylamine / dichloromethane / 2 h / 20 °C 3.1: potassium carbonate / N,N-dimethyl-formamide / 1 h / 90 °C 4.1: 1.5 h / 110 °C 4.2: 95 - 110 °C 5.1: acetonitrile / 20 °C / Inert atmosphere View Scheme

ethyl β-(3-chloro-2,4,5-trifluorophenyl)-β-oxopropionate (101987-86-4) → C24H26BClF2N4O8

Conditions	Yield
Multi-step reaction with 5 steps 1.1: acetic anhydride / 8 h / Reflux 2.1: triethylamine / dichloromethane / 2 h / 20 °C 3.1: potassium carbonate / N,N-dimethyl-formamide / 1 h / 90 °C 4.1: 1.5 h / 110 °C 4.2: 95 - 110 °C 5.1: acetonitrile / 20 °C / Inert atmosphere View Scheme

ethyl β-(3-chloro-2,4,5-trifluorophenyl)-β-oxopropionate (101987-86-4) → C29H28BClF2N4O8

Conditions	Yield
Multi-step reaction with 5 steps 1.1: acetic anhydride / 8 h / Reflux 2.1: triethylamine / dichloromethane / 2 h / 20 °C 3.1: potassium carbonate / N,N-dimethyl-formamide / 1 h / 90 °C 4.1: 1.5 h / 110 °C 4.2: 95 - 110 °C 5.1: acetonitrile / 20 °C / Inert atmosphere View Scheme

ethyl β-(3-chloro-2,4,5-trifluorophenyl)-β-oxopropionate (101987-86-4) + orthoformic acid triethyl ester (122-51-0) → ethyl 3-ethoxy-2-(3-chloro-2,4,5-trifluorobenzoyl)acrylate

Conditions	Yield
With acetic anhydride for 8h; Reflux;
With acetic anhydride for 8h; Reflux;
With acetic anhydride at 139℃; for 3h;
at 120 - 130℃; for 4h;

ethyl β-(3-chloro-2,4,5-trifluorophenyl)-β-oxopropionate (101987-86-4) → ethyl 3-[(6-amino-3,5-difluoropyridin-2-yl)amino]-2-(3-chloro-2,4,5-trifluorobenzoyl)acrylate

Conditions	Yield
Multi-step reaction with 2 steps 1: acetic anhydride / 8 h / Reflux 2: 1-methyl-pyrrolidin-2-one; acetonitrile / 6 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: acetic anhydride / 3 h / 139 °C 2: 1-methyl-pyrrolidin-2-one; acetonitrile / 1 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: 4 h / 120 - 130 °C 2: acetonitrile / 10 - 30 °C View Scheme

ethyl β-(3-chloro-2,4,5-trifluorophenyl)-β-oxopropionate (101987-86-4) → 1-(6-amino-3,5-difluoro-2-pyridyl)-8-chloro-6-fluoro-1,4-dihydro-7-fluoro-4-oxo-3-quinolinecarboxylic acid ethyl ester (189279-51-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: acetic anhydride / 8 h / Reflux 2: 1-methyl-pyrrolidin-2-one; acetonitrile / 6 h / 20 °C 3: potassium carbonate / butanone / 5 h / 60 °C View Scheme
Multi-step reaction with 3 steps 1: acetic anhydride / 3 h / 139 °C 2: 1-methyl-pyrrolidin-2-one; acetonitrile / 1 h / 20 °C 3: 1,8-diazabicyclo[5.4.0]undec-7-ene; lithium chloride / N,N-dimethyl-formamide / 2 h / 20 °C / Cooling with ice View Scheme
Multi-step reaction with 3 steps 1: 4 h / 120 - 130 °C 2: acetonitrile / 10 - 30 °C 3: potassium carbonate / N,N-dimethyl-formamide View Scheme

ethyl β-(3-chloro-2,4,5-trifluorophenyl)-β-oxopropionate (101987-86-4) → 1-(6-amino-3,5-difluoro-2-pyridinyl)-8-chloro-6,7-difluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid (189279-53-6)

Conditions	Yield
Multi-step reaction with 4 steps 1: acetic anhydride / 8 h / Reflux 2: 1-methyl-pyrrolidin-2-one; acetonitrile / 6 h / 20 °C 3: potassium carbonate / butanone / 5 h / 60 °C 4: acetic acid; hydrogenchloride / water / 1.5 h / 95 °C View Scheme
Multi-step reaction with 4 steps 1: 4 h / 120 - 130 °C 2: acetonitrile / 10 - 30 °C 3: potassium carbonate / N,N-dimethyl-formamide 4: hydrogenchloride; formic acid View Scheme

ethyl β-(3-chloro-2,4,5-trifluorophenyl)-β-oxopropionate (101987-86-4) → C23H22ClF3N6O4

Conditions	Yield
Multi-step reaction with 4 steps 1: acetic anhydride / 8 h / Reflux 2: 1-methyl-pyrrolidin-2-one; acetonitrile / 6 h / 20 °C 3: potassium carbonate / butanone / 5 h / 60 °C 4: lithium bromide; 1,8-diazabicyclo[5.4.0]undec-7-ene / dimethyl sulfoxide / 100 °C / Inert atmosphere View Scheme

Upstream product

• 101513-78-4 3-Chloro-2,4,5-trifluorobenzoyl chloride 
• 101513-77-3 3-Chloro-2,4,5-trifluorobenzoic acid 
• 1071-46-1 hydrogen ethyl malonate 
• 6148-64-7 ethyl potassium malonate 

Downstream Products

• 127254-12-0 sitafloxacin 
• 127199-27-3 8-chloro-6,7-difluoro-1-[(1R,2S)-cis-2-fluoro-1-cyclopropyl]-1,4-dihydro-4-oxoquinoline-3-carboxylic acid 
• 189279-58-1 delafloxacin 
• 208166-16-9 ethyl 8-chloro-6,7-difluoro-1-(4-fluoro-3-methoxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxylate 
• 197520-73-3 ethyl 1-(5-tert-butoxycarbonylamino-2,4-difluorophenyl)-8-chloro-6,7-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate 

Relevant articles and documents

A safe, economical method for the preparation of β-oxo esters

A high yield, economical method for preparation of β-oxo esters has been developed involving the reaction of acid chlorides with potassium ethyl malonate using a magnesium chloride-triethylamine base system in either acetonitrile or ethyl acetate solvents. The method is suitable for the preparation of high purity β-oxo esters in the laboratory and also in large scale production.

Process for the synthesis of 3-chloro-2,4,5-trifluorobenzoic acid

An improved process for the preparation of 3-chloro-2,4,5-trifluorobenzoic acid is described which involves reaction of a diester of 3,4,5,6-tetrafluoro-1,2-benzenedicarboxylic acid with a substituted amine to afford 3-amino-2,4,5-trifluorobenzoic acid followed by subsequent conversion of the amio intermediate into 3-chloro-2,4,5-trifluorobenzoic acid.