888327-36-4

Basic information

• Product Name: 2-Bromo-5-trifluoromethoxypyridine
• Synonyms: 2-Bromo-5-trifluoromethoxypyridine;Pyridine,2-bromo-5-(trifluoromethoxy)-;2-Bromo-5-(trifluoromethoxy)
• CAS NO: 888327-36-4
• Molecular Formula: C₆H₃BrF₃NO
• Molecular Weight: 242
• Mol File: 888327-36-4.mol
• Article Data: 5

Chemical Properties

• Boiling Point: 194.1 °C at 760 mmHg
• Flash Point: 71.2 °C
• Appearance: /
• Density: 1.737 g/cm³
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• PKA: -3.55±0.10(Predicted)
• CAS DataBase Reference: 2-Bromo-5-trifluoromethoxypyridine(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Bromo-5-trifluoromethoxypyridine(888327-36-4)
• EPA Substance Registry System: 2-Bromo-5-trifluoromethoxypyridine(888327-36-4)

Safety Data

• Statements: 43
• Safety Statements: 36/37
• RIDADR: 2810
• HazardClass: 6.1
• PackingGroup: Ⅲ
• Hazardous Substances Data: 888327-36-4(Hazardous Substances Data)

Usage

General Description

2-Bromo-5-trifluoromethoxypyridine is a chemical compound with the molecular formula C6H3BrF3NO. It is a pyridine derivative that is commonly used as a building block in organic synthesis. 2-Bromo-5-trifluoromethoxypyridine is characterized by the presence of a bromine atom and three trifluoromethoxy groups attached to a pyridine ring. It is primarily used as a reagent in the pharmaceutical and agrochemical industries for the production of various compounds. 2-Bromo-5-trifluoromethoxypyridine is known for its unique chemical properties, making it useful in the development of new drugs and crop protection products. Due to its versatility, this compound has gained significant importance in the field of organic chemistry and chemical research.

Synthetic route

2-chloro-5-(trifluoromethoxy)pyridine (1206972-45-3) → 2-bromo-5-(trifluoromethoxy)pyridine (888327-36-4)

Conditions	Yield
With trimethylsilyl bromide In propiononitrile for 24h; Reflux;	81%
With trimethylsilyl bromide In propiononitrile at 100℃; for 72h;	81%

6-bromo-pyridin-3-ol (55717-45-8) + tetrachloromethane (56-23-5) → 2-bromo-5-(trifluoromethoxy)pyridine (888327-36-4)

Conditions	Yield
Stage #1: 6-bromo-pyridin-3-ol; tetrachloromethane With antimony pentafluoride at 150℃; for 8h; Stage #2: With potassium hydroxide In water	2.9%

6-bromopyridin-3-ylboronic acid (223463-14-7) → 2-bromo-5-(trifluoromethoxy)pyridine (888327-36-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: dihydrogen peroxide; acetic acid / tetrahydrofuran / 0 - 20 °C 2: antimony pentafluoride / 8 h / 150 °C View Scheme

2-bromo-5-(trifluoromethoxy)pyridine (888327-36-4) + trifluoroacetic anhydride (407-25-0) → 2-bromo-5-(trifluoromethoxy)pyridin-1-ium-1-olate

Conditions	Yield
With dihydrogen peroxide In dichloromethane; water at 0℃; for 18h;	100%

2-bromo-5-(trifluoromethoxy)pyridine (888327-36-4) + 2,2-dimethyl-1-(2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-(pyrimidin-5-yl)propan-1-ol → 2,2-dimethyl-1-(2-methyl-4-(5-(trifluoromethoxy)pyridin-2-yl)phenyl)-1-(pyrimidin-5-yl)propan-1-ol

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In water; N,N-dimethyl-formamide at 120℃; for 0.5h; Suzuki Coupling; Inert atmosphere; Microwave irradiation;	93%

2-bromo-5-(trifluoromethoxy)pyridine (888327-36-4) + Ethyl bromodifluoroacetate (667-27-6) → ethyl 2,2-difluoro-2-(5-(trifluoromethoxy)pyridin-2-yl)acetate

Conditions	Yield
With copper In dimethyl sulfoxide at 80℃;	62%

2-bromo-5-(trifluoromethoxy)pyridine (888327-36-4) + carbon dioxide (124-38-9) → 5-(trifluoromethoxy)picolinic acid

Conditions	Yield
Stage #1: 2-bromo-5-(trifluoromethoxy)pyridine With n-butyllithium In hexane; toluene at -100 - -78℃; Stage #2: carbon dioxide In hexane; toluene Stage #3: With hydrogenchloride In water pH=4;	60%
Stage #1: 2-bromo-5-(trifluoromethoxy)pyridine With n-butyllithium In hexane; toluene at -78℃; for 2h; Stage #2: carbon dioxide In hexane; toluene Stage #3: With hydrogenchloride In hexane; water; toluene pH=4;	60%

2-bromo-5-(trifluoromethoxy)pyridine (888327-36-4) + ethyl (2E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate (1009307-13-4) → (E)-ethyl 3-(5-(trifluoromethoxy)pyridin-2-yl)acrylate

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate In 1,2-dimethoxyethane; water at 110℃; for 0.5h; Microwave irradiation; Sealed tube; Inert atmosphere;	56%
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate In 1,2-dimethoxyethane; water at 110℃; for 0.5h; Microwave irradiation;	56%

3-bromo-1H-1,2,4-triazole (7343-33-1) + 2-bromo-5-(trifluoromethoxy)pyridine (888327-36-4) → 2-(3-bromo-1H-1,2,4-triazol-1-yl)-5-(trifluoromethoxy)pyridine

Conditions	Yield
With copper(l) iodide; caesium carbonate In N,N-dimethyl-formamide at 100℃; for 1h; Inert atmosphere; Microwave irradiation;	31%
With copper(l) iodide; caesium carbonate In N,N-dimethyl-formamide at 100℃; for 1h; Sealed tube; Microwave irradiation;	31%

2-bromo-5-(trifluoromethoxy)pyridine (888327-36-4) + methyl 5-chloro-2-hydroxybenzoate (4068-78-4) → methyl 5-chloro-2-[[5-(trifluoromethoxy)-2-pyridyl]oxy]benzoate

Conditions	Yield
With 2-Picolinic acid; potassium phosphate; copper(l) iodide In dimethyl sulfoxide at 80℃; for 19h; Inert atmosphere;	31%

2-bromo-5-(trifluoromethoxy)pyridine (888327-36-4) + 1-t-Butoxycarbonylpiperazine (57260-71-6) → tert-butyl 4-[5-(trifluoromethoxy)pyridin-2-yl]piperazine-1-carboxylate

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate In toluene at 80℃; for 16h;	28%

2-bromo-5-(trifluoromethoxy)pyridine (888327-36-4) + C14H20N2O3 → C20H22F3N3O4

Conditions	Yield
With 15-crown-5; sodium hydride In N,N-dimethyl-formamide; mineral oil at 80℃; for 16h;	19%

5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)oxazole (942070-84-0) + 2-bromo-5-(trifluoromethoxy)pyridine (888327-36-4) → 5-(5-(trifluoromethoxy)pyridin-2-yl)oxazole

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In tetrahydrofuran for 16h; Suzuki Coupling; Reflux;	5.1%

2-bromo-5-(trifluoromethoxy)pyridine (888327-36-4) + N-(2-amino-2-methylcyclopentyl)-2-(2H-1,2,3-triazol-2-yl)benzamide hydrochloride → N-(2-methyl-2-{[5-(trifluoromethoxy)pyridin-2-yl]amino}cyclopentyl)-2-(2H-1,2,3-triazol-2-yl)benzamide

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate In toluene at 140℃; for 17h; Inert atmosphere;

2-bromo-5-(trifluoromethoxy)pyridine (888327-36-4) + N-[(1S,2S)-2-aminocyclopentyl]-2-(2H-1,2,3-triazol-2-yl)benzamide hydrochloride → 2-(2H-1,2,3-triazol-2-yl)-N-[(1S,2S)-2-{[5-(trifluoromethoxy)pyridin-2-yl]amino}cyclopentyl]benzamide

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate In toluene at 110℃; for 17h; Sealed tube; Inert atmosphere;

2-bromo-5-(trifluoromethoxy)pyridine (888327-36-4) + N-[(1S,2S)-2-aminocyclopentyl]-5-chloro-2-(2H-1,2,3-triazol-2-yl)benzamide hydrochloride → 5-chloro-2-(2H-1,2,3-triazol-2-yl)-N-[(1S,2S)-2-{[5-(trifluoromethoxy)pyridin-2-yl]amino}cyclopentyl]benzamide

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); potassium tert-butylate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In toluene at 120℃; for 0.25h; Inert atmosphere;

2-bromo-5-(trifluoromethoxy)pyridine (888327-36-4) + N-[(1S,2S)-2-amino-4,4-difluorocyclopentyl]-2-(2H-1,2,3-triazol-2-yl)benzamide → N-[(1S,2S)-4,4-difluoro-2-{[5-(trifluoromethoxy)pyridin-2-yl]amino}cyclopentyl]-2-(2H-1,2,3-triazol-2-yl)benzamide

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate In toluene at 120℃; for 17h; Inert atmosphere;

2-bromo-5-(trifluoromethoxy)pyridine (888327-36-4) → 2,2-difluoro-2-(5-(trifluoromethoxy)pyridin-2-yl)ethanol

Conditions	Yield
Multi-step reaction with 2 steps 1: copper / dimethyl sulfoxide / 80 °C 2: sodium tetrahydroborate; ethanol / 0.5 h / 20 °C View Scheme

2-bromo-5-(trifluoromethoxy)pyridine (888327-36-4) → 2,2-difluoro-2-(5-(trifluoromethoxy)pyridin-2-yl)ethyltrifluoromethanesulfonate

Conditions	Yield
Multi-step reaction with 3 steps 1: copper / dimethyl sulfoxide / 80 °C 2: sodium tetrahydroborate; ethanol / 0.5 h / 20 °C 3: N-ethyl-N,N-diisopropylamine / diethyl ether / 1 h / 0 - 20 °C / Inert atmosphere View Scheme

2-bromo-5-(trifluoromethoxy)pyridine (888327-36-4) → N-(1-(2,2-difluoro-2-(5-(trifluoromethoxy)pyridin-2-yl)ethyl)piperidin-4-yl)-7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine

Conditions	Yield
Multi-step reaction with 4 steps 1: copper / dimethyl sulfoxide / 80 °C 2: sodium tetrahydroborate; ethanol / 0.5 h / 20 °C 3: N-ethyl-N,N-diisopropylamine / diethyl ether / 1 h / 0 - 20 °C / Inert atmosphere 4: N-ethyl-N,N-diisopropylamine / dichloromethane; N,N-dimethyl-formamide / 60 °C View Scheme

2-bromo-5-(trifluoromethoxy)pyridine (888327-36-4) → N-(1-(2,2-difluoro-2-(5-(trifluoromethoxy)pyridin-2-yl)ethyl)piperidin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine

Conditions	Yield
Multi-step reaction with 5 steps 1: copper / dimethyl sulfoxide / 80 °C 2: sodium tetrahydroborate; ethanol / 0.5 h / 20 °C 3: N-ethyl-N,N-diisopropylamine / diethyl ether / 1 h / 0 - 20 °C / Inert atmosphere 4: N-ethyl-N,N-diisopropylamine / dichloromethane; N,N-dimethyl-formamide / 60 °C 5: sodium hydroxide / water; tetrahydrofuran / 3 h / 60 °C View Scheme

2-bromo-5-(trifluoromethoxy)pyridine (888327-36-4) → N-(1-(2,2-difluoro-2-(5-(trifluoromethoxy)pyridin-2-yl)ethyl)piperidin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride

Conditions

Yield

Multi-step reaction with 6 steps 1: copper / dimethyl sulfoxide / 80 °C 2: sodium tetrahydroborate; ethanol / 0.5 h / 20 °C 3: N-ethyl-N,N-diisopropylamine / diethyl ether / 1 h / 0 - 20 °C / Inert atmosphere 4: N-ethyl-N,N-diisopropylamine / dichloromethane; N,N-dimethyl-formamide / 60 °C 5: sodium hydroxide / water; tetrahydrofuran / 3 h / 60 °C 6: hydrogenchloride / methanol / 0.5 h / 20 °C View Scheme

2-bromo-5-(trifluoromethoxy)pyridine (888327-36-4) + N-[2-(1-benzylpiperidin-4-yl)ethyl]piperidine-4-carboxamide → N-[2-(1-benzylpiperidin-4-yl)ethyl]-1-[5-(trifluoromethoxy)pyridin-2-yl]piperidine-4-carboxamide

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate In toluene at 100℃;

2-bromo-5-(trifluoromethoxy)pyridine (888327-36-4) → 6-bromo-(3-trifluoromethoxy)pyridine-2-carbonitrile

Conditions	Yield
Multi-step reaction with 2 steps 1: dihydrogen peroxide / dichloromethane; water / 18 h / 0 °C 2: triethylamine / acetonitrile / 40 h / 80 °C View Scheme

2-bromo-5-(trifluoromethoxy)pyridine (888327-36-4) → 1-[5-(trifluoromethoxy)pyridin-2-yl]piperazine

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium t-butanolate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; tris-(dibenzylideneacetone)dipalladium(0) / toluene / 16 h / 80 °C 2: hydrogenchloride / water; 1,4-dioxane / 4 h / 20 °C View Scheme

2-bromo-5-(trifluoromethoxy)pyridine (888327-36-4) → N-[5-[(tert-butyldimethylsilyl)oxy]pyridin-2-yl]-4-[5-(trifluoromethoxy)pyridin-2-yl]piperazine-1-carboxamide

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium t-butanolate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; tris-(dibenzylideneacetone)dipalladium(0) / toluene / 16 h / 80 °C 2: hydrogenchloride / water; 1,4-dioxane / 4 h / 20 °C 3: triethylamine / dichloromethane / 16 h / 20 °C View Scheme

2-bromo-5-(trifluoromethoxy)pyridine (888327-36-4) → N-(5-hydroxypyridin-2-yl)-4-[5-(trifluoromethoxy)pyridin-2-yl]piperazine-1-carboxamide

Conditions	Yield
Multi-step reaction with 4 steps 1: sodium t-butanolate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; tris-(dibenzylideneacetone)dipalladium(0) / toluene / 16 h / 80 °C 2: hydrogenchloride / water; 1,4-dioxane / 4 h / 20 °C 3: triethylamine / dichloromethane / 16 h / 20 °C 4: hydrogenchloride / water; tetrahydrofuran / 2 h / 20 °C View Scheme

2-bromo-5-(trifluoromethoxy)pyridine (888327-36-4) → 5-(trifluoromethoxy)-2-(3-vinyl-1H-1,2,4-triazol-1-yl)pyridine

Conditions	Yield
Multi-step reaction with 2 steps 1: caesium carbonate; copper(l) iodide / N,N-dimethyl-formamide / 1 h / 100 °C / Sealed tube; Microwave irradiation 2: potassium carbonate; tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide; water / 0.5 h / 90 °C / Sealed tube; Microwave irradiation View Scheme

2-bromo-5-(trifluoromethoxy)pyridine (888327-36-4) + 4,4-difluoroazepane (1094073-72-9) → 4,4-difluoro-1-(5-(trifluoromethoxy)pyridin-2-yl)azepane

Conditions	Yield
With [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate; sodium t-butanolate In tetrahydrofuran at 60℃; for 12h; Inert atmosphere;
With [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate; sodium t-butanolate In tetrahydrofuran at 25 - 60℃; for 12h; Inert atmosphere;

Upstream product

• 55717-45-8 6-bromo-pyridin-3-ol 
• 56-23-5 tetrachloromethane 
• 223463-14-7 6-bromopyridin-3-ylboronic acid 
• 1206972-45-3 2-chloro-5-(trifluoromethoxy)pyridine 

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