759-67-1

Basic information

• Product Name: Ethyl 2-fluoro-3-oxopentanoate
• Synonyms: 2-FLUORO-3-OXO-PENTANOIC ACID ETHYL ESTER;ETHYL 2-FLUORO-3-OXOPENTANOATE;Ethyl2-fluoro-3-oxovalerate;ETHYL2-FLUORO-3-OXOPENTANOA;6-AMino-hexan-l-ol
• CAS NO: 759-67-1
• Molecular Formula: C₇H₁₁FO₃
• Molecular Weight: 162.16
• EINECS: 1592732-453-0
• Mol File: 759-67-1.mol
• Article Data: 8

Chemical Properties

• Boiling Point: 191.7 °C at 760 mmHg
• Flash Point: 68.2 °C
• Appearance: /
• Density: 1.077 g/cm³
• Refractive Index: 1.398
• PKA: 9.14±0.46(Predicted)
• CAS DataBase Reference: Ethyl 2-fluoro-3-oxopentanoate(CAS DataBase Reference)
• NIST Chemistry Reference: Ethyl 2-fluoro-3-oxopentanoate(759-67-1)
• EPA Substance Registry System: Ethyl 2-fluoro-3-oxopentanoate(759-67-1)

Safety Data

• Hazardous Substances Data: 759-67-1(Hazardous Substances Data)

Usage

Description

Ethyl 2-fluoro-3-oxopentanoate is an ester organic compound characterized by the presence of a fluorine atom and a ketone group within its molecular structure. It is known for its unique chemical properties and potential applications in various fields.

Uses

Used in Pharmaceutical Industry:
Ethyl 2-fluoro-3-oxopentanoate is used as a pharmaceutical intermediate for the synthesis of various medicinal compounds. Its unique structure allows it to serve as a key building block in the development of new drugs, particularly those targeting specific biological pathways or receptors.
Used in Chemical Synthesis:
In the field of chemical synthesis, Ethyl 2-fluoro-3-oxopentanoate can be utilized as a versatile reagent or precursor in the preparation of a wide range of organic compounds. Its fluorinated nature and ketone functionality make it a valuable component in the synthesis of specialty chemicals, agrochemicals, and other advanced materials.
Used in Research and Development:
Ethyl 2-fluoro-3-oxopentanoate is also employed in research and development settings, where it can be used to explore novel chemical reactions, investigate the effects of fluorination on molecular properties, and develop new synthetic methodologies. Its unique structure and reactivity make it an interesting target for academic and industrial research efforts.

InChI:InChI=1/C7H11FO3/c1-3-5(9)6(8)7(10)11-4-2/h6H,3-4H2,1-2H3

Synthetic route

2-fluoro-3-oxopentanoic acid-O3,O4-diacetic acid borate + propionyl chloride (79-03-8) → 2-fluoro-3-oxopentanoic acid ethyl ester (759-67-1)

Conditions	Yield
Reflux;	94.6%

ethyl propanoylacetate (4949-44-4) → 2-fluoro-3-oxopentanoic acid ethyl ester (759-67-1)

Conditions	Yield
With Selectfluor In acetonitrile at 50℃; Inert atmosphere;	86%

ethyl 2-fluoroacetate (459-72-3) + propionyl chloride (79-03-8) → 2-fluoro-3-oxopentanoic acid ethyl ester (759-67-1)

Conditions	Yield
With sodium ethanolate; triethylamine In tetrahydrofuran at 15℃; for 16h; Solvent; Time; Temperature; Reagent/catalyst;	85%
With sodium ethanolate; triethylamine In tetrachloromethane at 5 - 25℃; for 16h;

ethyl-2-fluoroacetoacetate (1522-41-4) + methyl iodide (74-88-4) → 2-fluoro-3-oxopentanoic acid ethyl ester (759-67-1)

Conditions	Yield
Stage #1: ethyl-2-fluoroacetoacetate With lithium diisopropyl amide In tetrahydrofuran at 0℃; for 1h; Stage #2: methyl iodide In tetrahydrofuran at -78 - 20℃; for 14h;	59%

ethyl 2-fluoroacetate (459-72-3) → 2-fluoro-3-oxopentanoic acid ethyl ester (759-67-1)

Conditions	Yield
With diethyl ether; sodium hydride Erwaermen des Reaktionsgemisches mit Propionylchlorid;

ethyl bromofluoroacetate (401-55-8) + propionyl chloride (79-03-8) → 2-fluoro-3-oxopentanoic acid ethyl ester (759-67-1)

Conditions	Yield
Yield given. Multistep reaction;

Tributyl-(1-ethoxycarbonyl-1-fluoro-2-oxo-butyl)-phosphonium; chloride → 2-fluoro-3-oxopentanoic acid ethyl ester (759-67-1)

Conditions	Yield
With sodium hydrogencarbonate In tetrahydrofuran; water for 6h; Ambient temperature; Yield given;

ethyl 3-hydroxypent-4-enoate (38996-01-9) → ethyl α-fluoropropionylacetate (227184-02-3) + 2-fluoro-3-oxopentanoic acid ethyl ester (759-67-1) + C7H10F2O3 (1340481-55-1) + ethyl propanoylacetate (4949-44-4)

Conditions	Yield
With bis[dichloro(pentamethylcyclopentadienyl)iridium(III)]; Selectfluor In tetrahydrofuran; water regiospecific reaction;

4-penten-3-one (1629-58-9) + 2-fluoro-3-oxopentanoic acid ethyl ester (759-67-1) → 2-Fluoro-5-oxo-2-propionyl-heptanoic acid ethyl ester (102283-25-0)

Conditions	Yield
With potassium fluoride In sulfolane for 2h; Ambient temperature;	92%

2-fluoro-3-oxopentanoic acid ethyl ester (759-67-1) + methyl vinyl ketone (78-94-4) → 2-Fluoro-5-oxo-2-propionyl-hexanoic acid ethyl ester (102283-24-9)

Conditions	Yield
With potassium fluoride In sulfolane for 2h; Ambient temperature;	89%

2-fluoro-3-oxopentanoic acid ethyl ester (759-67-1) + di-tert-butyl-diazodicarboxylate (870-50-8) → C17H29FN2O7 (1179476-79-9)

Conditions	Yield
Stage #1: 2-fluoro-3-oxopentanoic acid ethyl ester With C40H48Br2F4N4Ni In toluene at 20℃; for 0.166667h; Stage #2: di-tert-butyl-diazodicarboxylate In toluene at 20℃; for 20h; enantioselective reaction;	85%

2-fluoro-3-oxopentanoic acid ethyl ester (759-67-1) + 2-azidobenzaldehyde (16714-25-3) → ethyl 2-ethyl-4-hydroxyquinoline-3-carboxylate (86540-36-5)

Conditions	Yield
With triethylamine; triphenylphosphine In acetonitrile at 95℃; for 12h; Knoevenagel Condensation;	83%

2-fluoro-3-oxopentanoic acid ethyl ester (759-67-1) + (E)-1-([1,1'-biphenyl]-2-yl)but-2-en-1-one → 2,5-dimethyl-[1,1':2',1''-terphenyl]-3-ol

Conditions	Yield
With caesium carbonate In acetonitrile at 125℃; for 5h;	83%

2-fluoro-3-oxopentanoic acid ethyl ester (759-67-1) + tert-butyl 5-methylene-2-oxo-1,3-oxazinane-3-carboxylate → ethyl 4-({[(tert-butoxy)carbonyl]amino}methyl)-2-fluoro-2-propanoylpent-4-enoate

Conditions	Yield
Stage #1: tert-butyl 5-methylene-2-oxo-1,3-oxazinane-3-carboxylate With O,O'-(1,1'-biphenyl-2,2'-diyl)-N,N'-diisopropylphosphoramidite; bis(dibenzylideneacetone)-palladium(0) In dichloromethane at 20℃; for 0.166667h; Inert atmosphere; Sealed tube; Stage #2: 2-fluoro-3-oxopentanoic acid ethyl ester In dichloromethane at 20℃; for 18h; Inert atmosphere; Sealed tube;	83%

2-fluoro-3-oxopentanoic acid ethyl ester (759-67-1) + (E)-1-(2-methoxyphenyl)but-2-en-1-one (40872-81-9) → 2'-methoxy-2,5-dimethyl-[1,1'-biphenyl]-3-ol

Conditions	Yield
With caesium carbonate In acetonitrile at 125℃; for 5h;	76%

2-fluoro-3-oxopentanoic acid ethyl ester (759-67-1) + 2,6-dimethoxy-4-methylphenol (6638-05-7) → ethyl 2-fluoro-2-(4-hydroxy-3,5-dimethoxybenzyl)-3-oxopentanoate

Conditions	Yield
With copper diacetate In acetonitrile at 70℃; for 2.5h;	73%

(E)-1-(naphthalen-1-yl)but-2-en-1-one (128113-46-2) + 2-fluoro-3-oxopentanoic acid ethyl ester (759-67-1) → 2,5-dimethyl-3-(naphthalen-1-yl)phenol

Conditions	Yield
With caesium carbonate In acetonitrile at 125℃; for 5h;	72%

chloro-trimethyl-silane (75-77-4) + 2-fluoro-3-oxopentanoic acid ethyl ester (759-67-1) → C10H19FO3Si (1257084-53-9)

Conditions	Yield
With triethylamine In benzene at 20℃; for 48h;	67%

2-fluoro-3-oxopentanoic acid ethyl ester (759-67-1) + urea (57-13-6) → C6H7FN2O2

Conditions	Yield
Stage #1: urea With sodium methylate In methanol at 20℃; for 0.5h; Stage #2: 2-fluoro-3-oxopentanoic acid ethyl ester In methanol for 2.5h; Reflux;	66.42%

2-fluoro-3-oxopentanoic acid ethyl ester (759-67-1) + (E)-1-(2-chlorophenyl)but-2-en-1-one (1313028-19-1) → 2'-chloro-2,5-dimethyl-[1,1'-biphenyl]-3-ol

Conditions	Yield
With caesium carbonate In acetonitrile at 125℃; for 5h;	63%

(E)-1-(o-tolyl)but-2-en-1-one + 2-fluoro-3-oxopentanoic acid ethyl ester (759-67-1) → 2,2',5-trimethyl-[1,1'-biphenyl]-3-ol

Conditions	Yield
With caesium carbonate In acetonitrile at 125℃; for 5h;	56%

2-fluoro-3-oxopentanoic acid ethyl ester (759-67-1) + (E)-1-(2-(trifluoromethyl)phenyl)but-2-en-1-one (1360924-07-7) → 2,5-dimethyl-2'-(trifluoromethyl)-[1,1'-biphenyl]-3-ol

Conditions	Yield
With caesium carbonate In acetonitrile at 125℃; for 5h;	33%

2-fluoro-3-oxopentanoic acid ethyl ester (759-67-1) + guanidine hydrochloride (50-01-1) → 6-ethyl-2-amino-5-fluoro-3H-pyrimidin-4-one (700-54-9)

Conditions	Yield
With methanol; sodium methylate

2-fluoro-3-oxopentanoic acid ethyl ester (759-67-1) + formamidine acetic acid (3473-63-0) → 6-Ethyl-5-fluoropyrimidin-4(3H)-one (137234-87-8)

Conditions	Yield
With methanol; sodium methylate Multistep reaction;

2-fluoro-3-oxopentanoic acid ethyl ester (759-67-1) → 4-chloro-5-fluoro-6-ethylpyrimidine (137234-74-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1) MeONa, MeOH 2: POCl3 / Heating View Scheme
Multi-step reaction with 2 steps 1: sodium methylate / methanol / 20 h / 15 °C 2: trichlorophosphate / 3 h / 60 °C View Scheme

2-fluoro-3-oxopentanoic acid ethyl ester (759-67-1) → (2S,3R)-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol

Conditions	Yield
Multi-step reaction with 4 steps 1: 1) MeONa, MeOH 2: POCl3 / Heating 3: LDA / tetrahydrofuran 4: H2, AcONa / Pd/C / ethanol / 20 °C View Scheme

2-fluoro-3-oxopentanoic acid ethyl ester (759-67-1) → voriconazole (137234-62-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: 1) MeONa, MeOH 2: POCl3 / Heating 3: LDA / tetrahydrofuran 4: H2, AcONa / Pd/C / ethanol / 20 °C View Scheme

2-fluoro-3-oxopentanoic acid ethyl ester (759-67-1) → (2R,3S/2S,3R)-3-(4-chloro-5-fluoropyrimidin-6-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol

Conditions	Yield
Multi-step reaction with 3 steps 1: 1) MeONa, MeOH 2: POCl3 / Heating 3: LDA / tetrahydrofuran View Scheme

2-fluoro-3-oxopentanoic acid ethyl ester (759-67-1) → (2S,3S)-3-(6-Chloro-5-fluoro-pyrimidin-4-yl)-2-(2,4-difluoro-phenyl)-1-[1,2,4]triazol-1-yl-butan-2-ol

Conditions	Yield
Multi-step reaction with 3 steps 1: 1) MeONa, MeOH 2: POCl3 / Heating 3: LDA / tetrahydrofuran View Scheme

2-fluoro-3-oxopentanoic acid ethyl ester (759-67-1) → C7H12FNO2

Conditions	Yield
With ammonia In formamide for 1h;

Upstream product

• 4949-44-4 ethyl propanoylacetate 
• 401-55-8 ethyl bromofluoroacetate 
• 79-03-8 propionyl chloride 
• 459-72-3 ethyl 2-fluoroacetate 
• 38996-01-9 ethyl 3-hydroxypent-4-enoate 
• 1522-41-4 ethyl-2-fluoroacetoacetate 
• 74-88-4 methyl iodide 

Downstream Products

• 188416-28-6 1-(4-chloro-5-fluoropyrimidin-6-yl)bromoethane 
• 137234-87-8 6-ethyl-5-fluoro-4-hydroxypyrimidine 
• 137234-62-9 voriconazole 
• 137234-63-0 (2S,3R)-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol 
• 137234-74-3 4-chloro-6-ethyl-5-fluoropyrimidine 
• 137234-87-8 6-Ethyl-5-fluoropyrimidin-4(3H)-one 
• 700-54-9 6-ethyl-2-amino-5-fluoro-3H-pyrimidin-4-one 

Relevant articles and documents

A Pd-Catalyzed [4 + 2] Annulation Approach to Fluorinated N-Heterocycles

3-Fluoro- and trifluoromethylthio-piperidines represent important building blocks for discovery chemistry. We report a simple and efficient method to access analogs of these compounds that are armed with rich functionality allowing them to be chemoselectively derivatized with high diastereocontrol.

Method for continuously preparing voriconazole intermediate ethyl 2-fluoro-3-oxopentanoate

The invention discloses a method for continuously preparing a voriconazole intermediate, namely ethyl 2-fluoro-3-oxopentanoate. The method comprises the following steps: feeding a reaction solvent, ethyl 2-fluoro-acetate, propionyl chloride and sodium hydrogen into a reaction kettle for a reaction, then adding boric acid and acid anhydride, feeding a reaction liquid into a centrifugal machine, continuously feeding a supernatant into the middle part of a rectifying tower for heating and rectifying, condensing light components at the top of the tower, allowing the condensed light components to flow back to the reaction kettle, and collecting a heavy component product from the bottom of the tower so as to obtain the voriconazole intermediate. According to the invention, boric acid and acid anhydride are added after the reaction is finished, so a reaction byproduct, namely 2-fluoro-3-oxopentanoic acid is converted into 2-fluoro-3-oxopentanoic acid-O3,O4-borodiacetate which can be easily separated from a main product, so the purity of the product is further improved; low-energy-consumption, simple, rapid and continuous production is realized; and the yield of the obtained reaction product ethyl 2-fluoro-3-oxopentanoate is greater than 90%, and the purity of the product is 98% or above.

A facile synthesis of α-fluoro ketones catalyzed by [Cp*IrCl2]2

Allylic alcohols are isomerized into enolates (enols) by [Cp*IrCl2]2. The enolates react with Selectfluor present in the reaction media. This method produces α-fluoro ketones as single constitutional isomers in high yields. Georg Thieme Verlag Stuttgart. New York.