72537-17-8

Basic information

• Product Name: 3-CHLORO-2-FLUORO-5-(TRIFLUOROMETHYL)PYRIDINE
• Synonyms: 3-CHLORO-2-FLUORO-5-(TRIFLUOROMETHYL)PYRIDINE;2-FLUORO-3-CHLORO-5-(TRIFLUOROMETHYL)PYRIDINE;CHLORO-2-FLUORO-5-(TRIFLUOROMETHYL)PYRIDINE;3-Chloro-2-fluoro-5-(trifluoromethyl)pyridine 98%
• CAS NO: 72537-17-8
• Molecular Formula: C₆H₂ClF₄N
• Molecular Weight: 199.53
• EINECS: 1312995-182-4
• Product Categories: Pyridines, Pyrimidines, Purines and Pteredines;Halides;Pyridines;C6Heterocyclic Building Blocks;Halogenated Heterocycles;Heterocyclic Building Blocks
• Mol File: 72537-17-8.mol
• Article Data: 9

Chemical Properties

• Melting Point: 16-20 °C(lit.)
• Boiling Point: 50-55 °C11 mm Hg(lit.)
• Flash Point: 125 °F
• Appearance: Colorless/Liquid
• Density: 1.524 g/mL at 25 °C(lit.)
• Vapor Pressure: 3.944mmHg at 25°C
• Refractive Index: n20/D 1.433(lit.)
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• CAS DataBase Reference: 3-CHLORO-2-FLUORO-5-(TRIFLUOROMETHYL)PYRIDINE(CAS DataBase Reference)
• NIST Chemistry Reference: 3-CHLORO-2-FLUORO-5-(TRIFLUOROMETHYL)PYRIDINE(72537-17-8)
• EPA Substance Registry System: 3-CHLORO-2-FLUORO-5-(TRIFLUOROMETHYL)PYRIDINE(72537-17-8)

Safety Data

• Hazard Codes: Xi
• Statements: 10-36/37/38
• Safety Statements: 26-36
• RIDADR: UN 1993 3/PG 3
• WGK Germany: 3
• HazardClass: 3.2
• PackingGroup: III
• Hazardous Substances Data: 72537-17-8(Hazardous Substances Data)

Usage

General Description

3-Chloro-2-fluoro-5-(trifluoromethyl)pyridine, a halogenated pyridine derivative, is a fluorinated building block. It participates in the synthesis of 2,3-difluoro-5-(trifluoromethyl)pyridine.

InChI:InChI=1/C6H2ClF4N/c7-4-1-3(6(9,10)11)2-12-5(4)8/h1-2H

Synthetic route

2,3-dichloro-5-trifluoromethylpyridine (69045-84-7) → 2-fluoro-3-chloro-5-(trifluoromethyl)pyridine (72537-17-8)

Conditions	Yield
With potassium carbonate; cesium fluoride In dimethyl sulfoxide at 120℃; under 18.7519 - 22.5023 Torr; for 4h; Product distribution / selectivity;	100%
With potassium carbonate; cesium fluoride In 1-methyl-pyrrolidin-2-one at 70℃; for 1 - 3h; Product distribution / selectivity;	98%
With potassium fluoride; N-benzyl-N,N,N-triethylammonium chloride In N,N-dimethyl acetamide at 170℃; for 5h; Temperature;	97%

2-amino-3-chloro-5-(trifluoromethyl)pyridine (79456-26-1) → 2-fluoro-3-chloro-5-(trifluoromethyl)pyridine (72537-17-8)

Conditions	Yield
With pyridine hydrogenfluoride; sodium nitrite 1.) O deg C, 20 min, 2.) 20 deg C, 1 h;	99%
With pyridine; hydrogen fluoride; sodium nitrite 1.) 0 deg C, 30 min; 2.) 20 deg C, 1 h; Yield given. Multistep reaction;

2,3-dichloro-5-(trichloromethyl)pyridine (69045-83-6) → 2-fluoro-3-chloro-5-(trifluoromethyl)pyridine (72537-17-8)

Conditions	Yield
Stage #1: 2,3-dichloro-5-(trichloromethyl)pyridine under 75007.5 Torr; for 6h; Autoclave; Inert atmosphere; Stage #2: With hydrogen fluoride at -5 - 185℃; for 12h; Temperature; Autoclave;	97.56%
With hydrogen fluoride; antimony pentafluoride at 180℃; under 45004.5 Torr; for 24h; Temperature; Pressure; Large scale;

2-fluoro-3-chloro-5-(trifluoromethyl)pyridine (72537-17-8) → 2-amino-3-chloro-5-(trifluoromethyl)pyridine (79456-26-1)

Conditions	Yield
With ammonia In tetrahydrofuran at 35℃; under 1950.2 Torr; for 28h; Product distribution / selectivity; Autoclave; Inert atmosphere;	99.5%
With acetamidine hydrochloride; sodium hydroxide In water; dimethyl sulfoxide at 130℃; for 24h; Schlenk technique; chemoselective reaction;	94%
With ammonia In tetrahydrofuran at 30℃; under 3750.38 - 6750.68 Torr; for 30h; Temperature; Pressure; Autoclave; Inert atmosphere;

2-fluoro-3-chloro-5-(trifluoromethyl)pyridine (72537-17-8) + (2,3-difluorophenyl)boronic acid (121219-16-7) → 3-(2,3-difluorophenyl)-2-fluoro-5-trifluoromethylpyridine

Conditions	Yield
With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate In toluene at 90℃; for 16h; Suzuki-Miyaura coupling;	96%

2-fluoro-3-chloro-5-(trifluoromethyl)pyridine (72537-17-8) + (2,3-dimethylphenyl)zinc chloride → 3-(2,3-dimethylphenyl)-2-fluoro-5-trifluoromethylpyridine

Conditions	Yield
With tris(dibenzylideneacetone)dipalladium (0); ruphos In tetrahydrofuran at 70℃; for 15h; Negishi coupling;	92%

acetamidine hydrochloride (124-42-5) + 2-fluoro-3-chloro-5-(trifluoromethyl)pyridine (72537-17-8) → N-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)acetamide

Conditions	Yield
With water; caesium carbonate In dimethyl sulfoxide at 90℃; for 18h; Schlenk technique; chemoselective reaction;	92%

2-fluoro-3-chloro-5-(trifluoromethyl)pyridine (72537-17-8) → 3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3)

Conditions	Yield
With potassium cyanide; Aliquat 336 In water at 30℃; for 5h;	90%
With sodium cyanide; tetrabutylammomium bromide at 20 - 25℃; for 23h;	82%

sodium cyanide (773837-37-9) + 2-fluoro-3-chloro-5-(trifluoromethyl)pyridine (72537-17-8) → 3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3)

Conditions	Yield
Stage #1: 2-fluoro-3-chloro-5-(trifluoromethyl)pyridine With dmap In acetone for 5h; Reflux; Large scale; Stage #2: sodium cyanide In chloroform; water at 20℃; for 2.5h; Large scale;	89%
dmap In water; propiononitrile at 20℃; for 5h;	83%
With tetrabutylammomium bromide In water; dimethyl sulfoxide at 45 - 50℃; Concentration;	74.3%
With N-benzyl-N,N,N-triethylammonium chloride at 20℃; for 10h; Temperature;	46.7 g

4,5-dibromo-2H-1,2,3-triazole (22300-52-3) + 2-fluoro-3-chloro-5-(trifluoromethyl)pyridine (72537-17-8) → C8H2Br2ClF3N4 (1192847-40-7)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 90℃; regioselective reaction;	89%

potassium cyanide + 1,2-dichloro-ethane (107-06-2) + 2-fluoro-3-chloro-5-(trifluoromethyl)pyridine (72537-17-8) → butanedinitrile (110-61-2) + 3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3)

Conditions	Yield
With dmap In water at 75 - 78℃; for 12h; Reagent/catalyst; Temperature;	A 81.8% B 86.7%

2-fluoro-3-chloro-5-(trifluoromethyl)pyridine (72537-17-8) + (R)-2-(4-hydroxyphenoxy)propionic acid (94050-90-5) + butan-1-ol (71-36-3) → haloxyf-ethoxyethyl (99320-80-6)

Conditions	Yield
Stage #1: 2-fluoro-3-chloro-5-(trifluoromethyl)pyridine; (R)-2-(4-hydroxyphenoxy)propionic acid With potassium phosphate; tetra-(n-butyl)ammonium iodide In N,N-dimethyl-formamide at 50 - 60℃; for 2h; Stage #2: With 1,3,5-trichloro-2,4,6-triazine In N,N-dimethyl-formamide at 5 - 25℃; for 1.16667h; Stage #3: butan-1-ol In N,N-dimethyl-formamide	86%

potassium cyanide (151-50-8) + 2-fluoro-3-chloro-5-(trifluoromethyl)pyridine (72537-17-8) → 3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3)

Conditions	Yield
In dimethyl sulfoxide at 30℃; for 0.833333h;	84%

cyclohexyl zinc iodide (121883-35-0) + 2-fluoro-3-chloro-5-(trifluoromethyl)pyridine (72537-17-8) → 3-cyclohexyl-2-fluoro-5-(trifluoromethyl)pyridine (1160556-51-3)

Conditions	Yield
With 2′-(dicyclohexylphophanyl)-N2,N2,N6,N6-tetramethyl[1,1′-biphenyl]-2,6-diamine; palladium diacetate In tetrahydrofuran; toluene at 60℃; for 1h; Negishi coupling reaction; Inert atmosphere;	84%

2-fluoro-3-chloro-5-(trifluoromethyl)pyridine (72537-17-8) → [1(2H)-3-chloro-5-(trifluoromethyl)-3'-chloro-5'-(trifluoromethyl)-2'-bipyridin]-2-one (96741-18-3)

Conditions	Yield
With water; sodium hydroxide In dimethyl sulfoxide at 110℃; for 12h;	83%

methanol (67-56-1) + 2-fluoro-3-chloro-5-(trifluoromethyl)pyridine (72537-17-8) + (R)-2-(4-hydroxyphenoxy)propionic acid (94050-90-5) → (R)-2-[4-[[3-chloro-5-(trifluoromethyl)-2-pyridinyl]oxy]phenoxy]propanoic acid methyl ester (72619-32-0)

Conditions	Yield
Stage #1: 2-fluoro-3-chloro-5-(trifluoromethyl)pyridine; (R)-2-(4-hydroxyphenoxy)propionic acid With potassium phosphate; tetra-(n-butyl)ammonium iodide In N,N-dimethyl-formamide at 50 - 60℃; for 2h; Stage #2: With 1,3,5-trichloro-2,4,6-triazine In N,N-dimethyl-formamide at 5 - 25℃; for 1.16667h; Stage #3: methanol In N,N-dimethyl-formamide	80%

furan-3-boronic acid (55552-70-0) + 2-fluoro-3-chloro-5-(trifluoromethyl)pyridine (72537-17-8) → 2-fluoro-3-(furan-3-yl)-5-(trifluoromethyl)pyridine (1251914-15-4)

Conditions	Yield
With potassium phosphate; chloro(2-dicyclohexylphosphino-2’,4’,6’-triisopropyl-1,1‘-biphenyl)[2-(2’-amino-1,1‘-biphenyl’)]palladium(II) In tetrahydrofuran; water at 40℃; for 0.5h; Suzuki-Miyaura cross-coupling; Inert atmosphere;	78%

2-ethoxy-ethanol (110-80-5) + 2-fluoro-3-chloro-5-(trifluoromethyl)pyridine (72537-17-8) + (R)-2-(4-hydroxyphenoxy)propionic acid (94050-90-5) → haloxyfop-etotyl

Conditions	Yield
Stage #1: 2-fluoro-3-chloro-5-(trifluoromethyl)pyridine; (R)-2-(4-hydroxyphenoxy)propionic acid With potassium phosphate; tetra-(n-butyl)ammonium iodide In N,N-dimethyl-formamide at 50 - 60℃; for 2h; Stage #2: With 1,3,5-trichloro-2,4,6-triazine In N,N-dimethyl-formamide at 5 - 25℃; for 1.16667h; Stage #3: 2-ethoxy-ethanol In N,N-dimethyl-formamide	78%

(+)-(1S,2R,4R)-tert-butyl 2-amino-7-azabicyclo[2.2.1]heptane-7-carboxylate (500556-90-1) + 2-fluoro-3-chloro-5-(trifluoromethyl)pyridine (72537-17-8) → (1S,2R,4R)-tert-butyl 2-((3-chloro-5-(trifluoromethyl)pyridin-2-yl)amino)-7-azabicyclo[2.2.1]heptane-7-carboxylate

Conditions	Yield
With triethylamine In acetonitrile for 16h; Microwave irradiation; Inert atmosphere; Reflux;	78%

Sesamol (533-31-3) + 2-fluoro-3-chloro-5-(trifluoromethyl)pyridine (72537-17-8) → 2-[5-(1,3-benzodioxolyl)oxy]-3-chloro-5-(trifluoromethyl)pyridine

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide at 20℃; for 4h;	77%

1-(1-Cyclohexen-1-yl)pyrrolidine (1125-99-1) + 2-fluoro-3-chloro-5-(trifluoromethyl)pyridine (72537-17-8) → 2-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]cyclohexanone (868234-81-5)

Conditions	Yield
at 20 - 100℃; for 84h; Neat (no solvent);	72%
Stage #1: 1-(1-Cyclohexen-1-yl)pyrrolidine; 2-fluoro-3-chloro-5-(trifluoromethyl)pyridine at 20 - 100℃; for 84h; Stage #2: With sulfuric acid In water	72%

hydroquinone (123-31-9) + 2-fluoro-3-chloro-5-(trifluoromethyl)pyridine (72537-17-8) → 2-(4'-hydroxyphenoxy)-3-chloro-5-trifluoromethylpyridine (69045-89-2)

Conditions	Yield
With sodium hydroxide In dimethyl sulfoxide	70%

2',4'-dihydroxy-4-acetophenone (89-84-9) + 2-fluoro-3-chloro-5-(trifluoromethyl)pyridine (72537-17-8) → 1-[4-((3-chloro-5-(trifluoromethyl)-2-pyridinyl)oxy)-2-hydroxyphenyl]ethanone (451456-58-9)

Conditions	Yield
With potassium carbonate In acetonitrile for 2h; Heating;	65%

methanol (67-56-1) + carbon monoxide (201230-82-2) + 2-fluoro-3-chloro-5-(trifluoromethyl)pyridine (72537-17-8) → methyl 2-methoxy-5-(trifluoromethyl)nicotinate + dimethyl 5-(trifluoromethyl)pyridine-2,3-dicarboxylate

Conditions	Yield
With dichloro[2,2'-bis(diphenylphosphino)-1,1'-binaphthyl]palladium(II); triethylamine at 100℃; under 2585.74 Torr; for 14h;	A 60% B 10%

(S)-tert-butyl 6-(aminomethyl)-5-azaspiro[2.4]heptane-5-carboxylate (1262397-26-1) + 2-fluoro-3-chloro-5-(trifluoromethyl)pyridine (72537-17-8) → C18H23ClF3N3O2 (1445595-86-7)

Conditions	Yield
With potassium carbonate In 1-methyl-pyrrolidin-2-one at 100 - 150℃; Microwave irradiation;	60%
With potassium carbonate In 1-methyl-pyrrolidin-2-one at 100 - 150℃; Microwave irradiation;	60%

4-(1-cyclohepten-1-yl)morpholine (7182-08-3) + 2-fluoro-3-chloro-5-(trifluoromethyl)pyridine (72537-17-8) → 2-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]cycloheptanone (868234-82-6)

Conditions	Yield
at 120℃; for 3h; Neat (no solvent);	58%
Stage #1: 4-(1-cyclohepten-1-yl)morpholine; 2-fluoro-3-chloro-5-(trifluoromethyl)pyridine at 120℃; for 3h; Stage #2: With sulfuric acid In water	58%

N,N-dimethyl-formamide (68-12-2, 33513-42-7) + 2-fluoro-3-chloro-5-(trifluoromethyl)pyridine (72537-17-8) → 3-chloro-N,N-dimethyl-5-(trifluoromethyl)pyridin-2-amine (157071-79-9)

Conditions	Yield
With potassium hydroxide In neat (no solvent) at 100℃; for 24h; Sealed tube; regioselective reaction;	57%

2-fluoro-3-chloro-5-(trifluoromethyl)pyridine (72537-17-8) → 3-chloro-2-[4-(prop-2-enyloxy)phenoxy]-5-(trifluoromethyl)pyridine (451456-48-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 70 percent / aq. NaOH / dimethylsulfoxide 2: 86 percent / K2CO3 / dimethylformamide / 0.5 h / 70 °C View Scheme

2-fluoro-3-chloro-5-(trifluoromethyl)pyridine (72537-17-8) → 4-[(3-chloro-5-(trifluoromethyl)-2-pyridinyl)oxy]-2-(hydroxymethyl)phenol (451456-45-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: 70 percent / aq. NaOH / dimethylsulfoxide 2: 57 percent / propanoic acid / benzene / 3 h / Heating 3: 82 percent / 30 percent H2O2 / tetrahydrofuran / 2 h / 20 °C View Scheme

2-fluoro-3-chloro-5-(trifluoromethyl)pyridine (72537-17-8) → 4-[(3-chloro-5-(trifluoromethyl)-2-pyridinyl)oxy]-2-(prop-2-enyl)phenol (451456-50-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: 70 percent / aq. NaOH / dimethylsulfoxide 2: 86 percent / K2CO3 / dimethylformamide / 0.5 h / 70 °C 3: 84 percent / 2 h / 210 - 215 °C View Scheme

Upstream product

• 69045-83-6 2,3-dichloro-5-(trichloromethyl)pyridine 
• 79456-26-1 2-amino-3-chloro-5-(trifluoromethyl)pyridine 
• 69045-84-7 2,3-dichloro-5-trifluoromethylpyridine 

Downstream Products

• 451456-58-9 1-[4-((3-chloro-5-(trifluoromethyl)-2-pyridinyl)oxy)-2-hydroxyphenyl]ethanone 
• 69045-89-2 2-(4'-hydroxyphenoxy)-3-chloro-5-trifluoromethylpyridine 
• 451456-48-7 3-chloro-2-[4-(prop-2-enyloxy)phenoxy]-5-(trifluoromethyl)pyridine 
• 451456-45-4 4-[(3-chloro-5-(trifluoromethyl)-2-pyridinyl)oxy]-2-(hydroxymethyl)phenol 
• 451456-50-1 4-[(3-chloro-5-(trifluoromethyl)-2-pyridinyl)oxy]-2-(prop-2-enyl)phenol 
• 451456-49-8 3-chloro-2-[4-(2-methylprop-2-enyloxy)phenoxy]-5-(trifluoromethyl)pyridine 
• 451456-53-4 4-(3-chloro-5-trifluoromethyl-pyridin-2-yloxy)-2-(2-methyl-oxiranylmethyl)-phenol 
• 451456-52-3 4-(3-chloro-5-trifluoromethyl-pyridin-2-yloxy)-2-oxiranylmethyl-phenol 
• 451456-51-2 4-[(3-chloro-5-(trifluoromethyl)-2-pyridinyl)oxy]-2-(2-methylprop-2-enyl)phenol 
• 451456-59-0 1-[4-((3-chloro-5-(trifluoromethyl)-2-pyridinyl)oxy)-2-(2-oxiranylmethoxy)phenyl]ethanone 
• 451456-44-3 6-[(3-chloro-5-(trifluoromethyl)-2-pyridinyl)oxy]-2-phenyl-4H-1,3,2-benzodioxaborinin 
• 451456-64-7 4-[(3-chloro-5-(trifluoromethyl)-2-pyridinyl)oxy]-2-[(2-methyl-2-oxiranyl)methoxy]phenyl acetate 
• 451456-63-6 1-[(4-(3-chloro-5-(trifluoromethyl)-2-pyridinyl)oxy)-2-((2-methyl-propenyl)oxy)phenyl]ethanone 
• 80194-70-3 3-chloro-2-cyano-5-(trifluoromethyl)pyridine 

Relevant articles and documents

Preparation method of 2-fluorine-3-chlorine-5-trifluoromethylpyridine

The invention relates to the technical field of chemical synthesis, and in particular discloses a preparation method of 2-fluorine-3-chlorine-5-trifluoromethylpyridine. The preparation method of the 2-fluorine-3-chlorine-5-trifluoromethylpyridine is characterized by comprising the following steps: taking 2-chlorine-5-trichloromethylpyridine as a raw material, taking tungsten hexachloride as a catalyst, heating and introducing chlorine to perform chlorination reaction, thereby obtaining 2,3-dichloro-5-trichloromethylpyridine; putting the 2,3-dichloro-5-trichloromethylpyridine into a fluorination kettle, adding antimony pentafluoride and anhydrous hydrogen fluoride, stirring and heating to perform reaction, cooling after reaction, washing with water, layering, feeding to a rectification kettle, and performing reduced-pressure rectification, thereby preparing the 2-fluorine-3-chlorine-5-trifluoromethylpyridine. The process is reliable, the raw materials are sufficient in the market and easily available, and the preparation method of the 2-fluorine-3-chlorine-5-trifluoromethylpyridine is low in production cost, simple in operation, high in yield and favorable for large-scale production.

A 2 - cyano - 3 - chloro - 5 - trifluoro methyl pyridine synthesis method (by machine translation)

The invention discloses a 2 - cyano - 3 - chloro - 5 - trifluoro methyl pyridine synthesis method, which belongs to the technical field of organic synthesis. The method includes the steps of: (1) to 2, 3 - dichloro - 5 - trifluoro methyl pyridine as raw material, in the solvent system is added in the catalyst, by fluorination synthesis of 2 - fluoro - 3 - chloro - 5 - trifluoro methyl pyridine, (2) in the step 1 of the 2 - fluoro - 3 - chloro - 5 - trifluoro methyl pyrrole cyanide reagent carbonitriding after adding, after the water washing, after the distillation, shall be 2 - cyano - 3 - chloro - 5 - trifluoro methyl pyridine. The purity of the product can reach 99.5%, the yield can be 90%, the reaction condition during the mild, easy to operate, and is suitable for large-scale production. (by machine translation)