31301-51-6

Basic information

• Product Name: 2-Chloro-5-fluoropyridine
• Synonyms: 2-CHLORO-5-FLUOROPYRIDINE;2-Chloro-5-fluoropyridine 98%;2-Chloro-5-fluoropyridine98%;2-Chloro-5-fluoropyridine ,96%;2-chloro-5-fluoridepyridine;5-Fluoro-2-chloropyridine;2-CHLORO-5-FLUOROPYPRIDINE;Pyridine, 2-chloro-5-fluoro-
• CAS NO: 31301-51-6
• Molecular Formula: C₅H₃ClFN
• Molecular Weight: 131.54
• Product Categories: Fluorin-contained pyridine series;Pyridine;pyridine derivative;Pyridines, Pyrimidines, Purines and Pteredines;Pyridines;Pyridines derivates;Chloropyridines;Fluoropyridines;Halopyridines;Boronic Acid;C5Heterocyclic Building Blocks;Halogenated Heterocycles;Heterocyclic Building Blocks;Variety of halogenated heterocyclic series;Building Blocks;C5;C5 to C6;Chemical Synthesis;Fluorinated Building Blocks;Halogenated Heterocycles;Heterocyclic Building Blocks;Heterocyclic Fluorinated Building Blocks;Other Fluorinated Heterocycles;Fluorine series
• Mol File: 31301-51-6.mol
• Article Data: 8

Chemical Properties

• Melting Point: 19℃
• Boiling Point: 74 °C / 38mmHg
• Flash Point: 108 °C
• Appearance: light yellow powder
• Density: 1.297 g/mL at 25 °C
• Vapor Pressure: 0.000629mmHg at 25°C
• Refractive Index: n20/D 1.503
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• PKA: -2.20±0.10(Predicted)
• CAS DataBase Reference: 2-Chloro-5-fluoropyridine(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Chloro-5-fluoropyridine(31301-51-6)
• EPA Substance Registry System: 2-Chloro-5-fluoropyridine(31301-51-6)

Safety Data

• Hazard Codes: Xn,Xi
• Statements: 10-22-37/38-41-36/37/38
• Safety Statements: 26-36/39-36
• RIDADR: UN 1993 3/PG 3
• WGK Germany: 3
• HazardClass: 3
• PackingGroup: III
• Hazardous Substances Data: 31301-51-6(Hazardous Substances Data)

Usage

Chemical Properties

Light yellow powder

InChI:InChI=1/C8H6F3NO2/c9-8(10,11)5-3-1-2-4(6(5)12)7(13)14/h1-3H,12H2,(H,13,14)

Synthetic route

5-bromo-2-chloropyridine (53939-30-3) → 2-chloro-5-fluoropyridine (31301-51-6)

Conditions	Yield
Stage #1: 5-bromo-2-chloropyridine With TurboGrignard In tetrahydrofuran; 1,4-dioxane at 0℃; Inert atmosphere; Stage #2: With N-fluorobis(benzenesulfon)imide In dichloromethane; octadecafluorodecahydronaphthalene (cis+trans) at -78 - 20℃; Inert atmosphere;	75%
Stage #1: 5-bromo-2-chloropyridine With TurboGrignard In tetrahydrofuran at 0℃; Inert atmosphere; Stage #2: With N-fluorobis(benzenesulfon)imide In dichloromethane; octadecafluorodecahydronaphthalene (cis+trans) at -78 - 25℃; Inert atmosphere;	75%

2-chloropyridine-5-yldiazonium tetrafluoroborate → 2-chloro-5-fluoropyridine (31301-51-6)

Conditions	Yield
In n-heptane for 3h; Heating;	70%
In n-heptane at 105℃; for 2h;
In n-heptane at 105℃; for 2h;

6-Chloro-pyridin-3-ylamine (5350-93-6) → 2-chloro-5-fluoropyridine (31301-51-6)

Conditions	Yield
With tert.-butylnitrite; boron trifluoride diethyl etherate In 1,2-dichloro-benzene at 105℃; for 0.75h; Balz-Schiemann Reaction;	36 %Spectr.

2-choro-5-iodopyridine (69045-79-0) → 2-chloro-5-fluoropyridine (31301-51-6)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0 - 20 °C 1.2: 0.5 h 2.1: copper(II) methanesulfonate; potassium fluoride; 18-crown-6 ether / N,N-dimethyl-formamide / 18 h / 60 °C View Scheme

C14H14ClIN(1+)*BF4(1-) → 2-chloro-5-fluoropyridine (31301-51-6)

Conditions	Yield
With potassium fluoride; 18-crown-6 ether; copper(II) methanesulfonate In N,N-dimethyl-formamide at 60℃; for 18h; Reagent/catalyst; Time; Solvent;	33 %Spectr.

5-[1-(methylsulfonimidoyl)ethyl]-2-(trifluoromethyl)pyridine (946578-43-4) + 2-chloro-5-fluoropyridine (31301-51-6) → 3-[1-ethyl(N-(2-(5-chloro)pyridine)-sulfoximinyl)(methyl)]-6-trifluoromethylpyridine (1106808-39-2)

Conditions	Yield
With caesium carbonate; palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In toluene at 150℃; for 0.5h; Microwave irradiation;	99%

2-chloro-5-fluoropyridine (31301-51-6) + trimethoxonium tetrafluoroborate (420-37-1) → C6H6ClFN(1+)*BF4(1-) (1622456-58-9)

Conditions	Yield
In dichloromethane at 20℃;	99%

piperidine (110-89-4) + 2-chloro-5-fluoropyridine (31301-51-6) → 5-fluoro-2-(piperidin-1-yl)pyridine

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; XPhos In toluene at 100℃; for 24h; Catalytic behavior; Reagent/catalyst; Inert atmosphere;	99%

2-chloro-5-fluoropyridine (31301-51-6) + 1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylic acid tert-butyl ester (930785-40-3) → tert-butyl 4-(5-fluoropyridin-2-yl)-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate

Conditions	Yield
With [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl) palladium(II) dichloride; caesium carbonate In toluene at 120℃; for 72h;	98%

2-chloro-5-fluoropyridine (31301-51-6) + phenylboronic acid (98-80-6) → 2-phenyl-5-fluoropyridine (512171-81-2)

Conditions	Yield
With C43H46ClF6N3Pd; potassium hydroxide In water; isopropyl alcohol at 80℃; for 2h; Suzuki-Miyaura Coupling; Inert atmosphere;	95%
With palladium diacetate; caesium carbonate; tricyclohexylphosphine tetrafluoroborate In 1,4-dioxane at 120℃; for 16h;

2-chloro-5-fluoropyridine (31301-51-6) → 5,5’-difluoro-2,2’-bipyridine (1041837-79-9)

Conditions	Yield
With potassium hydroxide In water; N,N-dimethyl-formamide at 45℃; for 24h; Ullmann Condensation; Inert atmosphere;	94%

1,2,4-Triazole (288-88-0) + 2-chloro-5-fluoropyridine (31301-51-6) → C7H5FN4

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide; mineral oil at 100℃; Inert atmosphere;	93%

2-chloro-5-fluoropyridine (31301-51-6) → 2-chloro-5-fluoropyridine 1-oxide (405230-79-7)

Conditions	Yield
With dihydrogen peroxide; trifluoroacetic acid at 70℃; for 16h; Inert atmosphere;	90%
Stage #1: 2-chloro-5-fluoropyridine With dihydrogen peroxide; trifluoroacetic acid In water at 70 - 75℃; Stage #2: With ammonium hydroxide In dichloromethane; water	74%
With dihydrogen peroxide; trifluoroacetic acid at 70℃;	71.2%

2-chloro-5-fluoropyridine (31301-51-6) + 2-methyl-1-tetralone (1590-08-5) → 2-(5-fluoropyridin-2-yl)-2-methyl-3,4-dihydronaphthalen-1(2H)-one

Conditions	Yield
With (R)-(-)-5,5’-bis(diphenyl;phosphine)-2,2,2’,2’-tetrafluoro-4,4’-bi-1,3-benzodioxole; bis(1,5-cyclooctadiene)nickel (0); sodium t-butanolate In toluene at 70℃; for 28h; Inert atmosphere; optical yield given as %ee; enantioselective reaction;	89%

2-chloro-5-fluoropyridine (31301-51-6) + 4-phenoxyphenylboronic acid (51067-38-0) → C17H12FNO

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In water; toluene at 110℃; for 48h; Suzuki Coupling; Inert atmosphere;	88.4%

2-chloro-5-fluoropyridine (31301-51-6) + 2,3-dihydro-2-methyl-1H-inden-1-one (17496-14-9) → 2-methyl-2-(5-flouropyridin-2-yl)-2,3-dihydro-1H-inden-1-one

Conditions	Yield
With (R)-(-)-5,5’-bis(diphenyl;phosphine)-2,2,2’,2’-tetrafluoro-4,4’-bi-1,3-benzodioxole; bis(1,5-cyclooctadiene)nickel (0); sodium t-butanolate In toluene at 70℃; for 28h; Inert atmosphere; optical yield given as %ee; enantioselective reaction;	86%

1H-imidazole (288-32-4) + 2-chloro-5-fluoropyridine (31301-51-6) → 2-(1H-imidazolyl)pyridine (25700-14-5)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20 - 100℃; Inert atmosphere;	86%

2-chloro-5-fluoropyridine (31301-51-6) + C15H24N2O → C20H26ClN3O

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; lithium hexamethyldisilazane at 90℃; for 16h; Inert atmosphere;	85.74%

2-chloro-5-fluoropyridine (31301-51-6) + 6,7,8,9-tetrahydro-8-methylpyrido[1,2-a]indol-9-one → C18H15FN2O

Conditions	Yield
With bis(1,5-cyclooctadiene)nickel (0); (R)-DIFLUOROPHOS; sodium t-butanolate In toluene at 85℃; for 48h; enantioselective reaction;	82%

2-chloro-5-fluoropyridine (31301-51-6) + (4-isopropylbenzaldehyde) (122-03-2) → (6-chloro-3-fluoropyridin-2-yl)(4-isopropylphenyl)methanol

Conditions	Yield
Stage #1: 2-chloro-5-fluoropyridine With sodium; diisopropylamine; isoprene In tetrahydrofuran at -78℃; for 0.000138889h; Flow reactor; Stage #2: (4-isopropylbenzaldehyde) In tetrahydrofuran Flow reactor;	77%

2-chloro-5-fluoropyridine (31301-51-6) + 1-phenyl-2-bromoethane (103-63-9) → 5-fluoro-2-phenethylpyridine

Conditions	Yield
Stage #1: 1-phenyl-2-bromoethane With iodine; magnesium In tetrahydrofuran at 0 - 80℃; for 0.5h; Inert atmosphere; Stage #2: 2-chloro-5-fluoropyridine With iron(III)-acetylacetonate In tetrahydrofuran; 1-methyl-pyrrolidin-2-one at 0 - 20℃; for 0.5h; Inert atmosphere;	77%

2-chloro-5-fluoropyridine (31301-51-6) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → 2-chloro-5-fluoroisonicotinaldehyde (884494-54-6)

Conditions	Yield
Stage #1: 2-chloro-5-fluoropyridine With lithium diisopropyl amide In tetrahydrofuran at -60℃; for 2h; Inert atmosphere; Stage #2: N,N-dimethyl-formamide In tetrahydrofuran at -60℃; for 2h;	74%
Stage #1: 2-chloro-5-fluoropyridine With n-butyllithium In tetrahydrofuran; hexane at -70℃; for 0.5h; Inert atmosphere; Stage #2: N,N-dimethyl-formamide In tetrahydrofuran; hexane at -70℃; for 1h;

3,6-diazabicyclo[3.1.1]heptane-6-carboxylic acid tert-butyl ester (869494-16-6) + 2-chloro-5-fluoropyridine (31301-51-6) → tert-butyl 3-(5-chloropyrazine-2-yl)-3,6-diazabicyclo[3.1.1]heptane-6-carboxylate

Conditions	Yield
In dimethyl sulfoxide at 120℃;	74%

2-chloro-5-fluoropyridine (31301-51-6) → 2-chloro-4-iodo-5-fluoropyridine (884494-49-9)

Conditions	Yield
Stage #1: 2-chloro-5-fluoropyridine With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 2h; Inert atmosphere; Stage #2: With iodine In tetrahydrofuran for 1h;	70%
Stage #1: 2-chloro-5-fluoropyridine With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 3h; Inert atmosphere; Stage #2: With iodine In tetrahydrofuran at -78℃; for 1h;	60%
Stage #1: 2-chloro-5-fluoropyridine With tert.-butyl lithium In tetrahydrofuran; pentane at -78℃; for 2h; Inert atmosphere; Stage #2: With iodine In tetrahydrofuran; pentane	39%

2-chloro-5-fluoropyridine (31301-51-6) → 2-chloro-5-fluoropyridin-4-ol

Conditions	Yield
Stage #1: 2-chloro-5-fluoropyridine With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 2.5h; Inert atmosphere; Stage #2: With Trimethyl borate In tetrahydrofuran at -78 - 20℃; for 2.33333h; Inert atmosphere; Stage #3: With dihydrogen peroxide; acetic acid In tetrahydrofuran at 0 - 20℃; Inert atmosphere;	68%

2-chloro-5-fluoropyridine (31301-51-6) + (RS)-2-(4-fluorophenyl)piperazine (65709-33-3) → C15H15F2N3

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); X-Phos; sodium t-butanolate In 1,4-dioxane at 80℃; for 2h; Inert atmosphere; Microwave irradiation;	67%
With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; XPhos In 1,4-dioxane at 80℃; for 2h; Inert atmosphere; Microwave irradiation;	67%

2-chloro-5-fluoropyridine (31301-51-6) + C11H13BrMgO2*ClLi → 4-(5-fluoropyridin-2-yl)phenyl pivalate

Conditions	Yield
With chromium dichloride In tetrahydrofuran at 25℃; for 0.25h; Inert atmosphere;	66%

4-carbethoxypiperidine (1126-09-6) + 2-chloro-5-fluoropyridine (31301-51-6) → 1-(5-fluoropyridin-2-yl)piperidine-4-carboxylic acid ethyl (1310820-59-7)

Conditions	Yield
With sodium t-butanolate; tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In toluene at 75℃; for 2h;	65%
With sodium t-butanolate; tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In toluene at 75℃; for 2h;	65%

benzoimidazole (51-17-2) + 2-chloro-5-fluoropyridine (31301-51-6) → 2-chloro-5-(1H-benzimidazol-1-yl)pyridine

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide at 70℃; for 24h; Inert atmosphere;	65%

2-chloro-5-fluoropyridine (31301-51-6) + N-tert-butoxycarbonyl-proline (15761-39-4) → tert-butyl 2-(5-fluoropyridin-2-yl)pyrrolidine-1-carboxylate

Conditions	Yield
With (1,2-dimethoxyethane)dichloronickel(II); [4,4’-bis(1,1-dimethylethyl)-2,2’-bipyridine-N1,N1‘]bis [3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-N]phenyl-C]iridium(III) hexafluorophosphate; caesium carbonate; 4,4'-di-tert-butyl-2,2'-bipyridine In N,N-dimethyl-formamide at 23℃; Irradiation;	64%

2-chloro-5-fluoropyridine (31301-51-6) → 6,6'-dichloro-3,3'-difluoro-2,2'-bipyridine

Conditions	Yield
Stage #1: 2-chloro-5-fluoropyridine With (2,2,6,6-tetramethylpiperidyl)2Mn*2MgCl2*4LiCl In tetrahydrofuran at 0℃; for 3h; Inert atmosphere; Schlenk technique; Stage #2: With chloranil In tetrahydrofuran at -40℃; for 0.5h; Inert atmosphere; Schlenk technique;	64%

2-chloro-5-fluoropyridine (31301-51-6) + 2,6-diazaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester hemioxylate (1041026-70-3) → tert-butyl 6-(5-fluoropyridin-2-yl)-2,6-diazaspiro[3.3]heptane-2-carboxylate

Conditions	Yield
With (2-dicyclohexylphosphino-2',6'-diisopropoxy-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) methanesulfonate; sodium t-butanolate In 1,4-dioxane at 120℃; for 5h;	62.2%

2-chloro-5-fluoropyridine (31301-51-6) + N-Methoxy-N-methylacetamide (78191-00-1) → 1-(2-chloro-5-fluoropyridin-4-yl)ethan-1-one (736990-31-1)

Conditions	Yield
Stage #1: 2-chloro-5-fluoropyridine With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Stage #2: N-Methoxy-N-methylacetamide In tetrahydrofuran; hexane at -78 - 20℃; for 1h;	61%

Upstream product

• 69045-79-0 2-choro-5-iodopyridine 
• 5350-93-6 6-Chloro-pyridin-3-ylamine 
• 53939-30-3 5-bromo-2-chloropyridine 

Downstream Products

• 512171-81-2 5-fluoro-2-phenylpyridine 
• 1335110-57-0 5-fluoro-2,4-diphenylpyridine 
• 145934-89-0 2-chloro-5-hydrazinylpyridine 
• 884494-74-0 2-chloro-5-fluoro-pyridine-4-carboxylic acid 
• 1211515-16-0 2-chloro-5-fluoro-4-methoxypyridine 
• 884494-54-6 2-chloro-5-fluoroisonicotinaldehyde 

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