50488-34-1

Basic information

• Product Name: 2-Bromo-4-(tert-butyl)pyridine
• Synonyms: 2-Bromo-4-(tert-butyl)pyridine
• CAS NO: 50488-34-1
• Molecular Formula: C₉H₁₂BrN
• Molecular Weight: 214.10228
• Mol File: 50488-34-1.mol
• Article Data: 7

Chemical Properties

• Boiling Point: 243.638 °C at 760 mmHg
• Flash Point: 101.149 °C
• Appearance: /
• Density: 1.293 g/cm³
• Vapor Pressure: 0.0495mmHg at 25°C
• Refractive Index: 1.521
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• PKA: 1.50±0.10(Predicted)
• CAS DataBase Reference: 2-Bromo-4-(tert-butyl)pyridine(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Bromo-4-(tert-butyl)pyridine(50488-34-1)
• EPA Substance Registry System: 2-Bromo-4-(tert-butyl)pyridine(50488-34-1)

Safety Data

• Hazardous Substances Data: 50488-34-1(Hazardous Substances Data)

Usage

General Description

2-Bromo-4-(tert-butyl)pyridine is a chemical compound known as an aromatic tertiary amine. This particular compound is characterized by a pyridine ring, which is a six-membered aromatic ring with a nitrogen atom, further substituted with a bromine atom and a tert-butyl group at positions 2 and 4 respectively. It is often used as a starting material or intermediate in organic synthesis, leading to more complex chemical structures. The exact properties such as melting point, boiling point and specific rotation of this compound can vary depending on the specific conditions, and may not be known. As with many organic compounds, care must be taken in handling this substance due to potential health hazards.

InChI:InChI=1/C9H12BrN/c1-9(2,3)7-4-5-11-8(10)6-7/h4-6H,1-3H3

Synthetic route

2-chloro-4-(1,1-dimethylethyl)pyridine (81167-60-4) → 2-bromo-4-(tert-butyl)pyridine (50488-34-1)

Conditions	Yield
With trimethylsilyl bromide; propiononitrile for 21h; Reflux;	100%
With trimethylsilyl bromide for 48h; Reflux;	80%

C12H12F6LiNO → 2-bromo-4-(tert-butyl)pyridine (50488-34-1)

Conditions	Yield
With 1,2-dibromo-1,1,2,2-tetrachloroethane In tetrahydrofuran; diethyl ether at -107℃;	50%

4-tert-butylpyridine (3978-81-2) → 2-bromo-4-(tert-butyl)pyridine (50488-34-1)

Conditions	Yield
Stage #1: 4-tert-butylpyridine With n-butyllithium; 2-(N,N-dimethylamino)ethanol at -5℃; for 1h; Inert atmosphere; Stage #2: With carbon tetrabromide at -78 - 20℃; Inert atmosphere;	45%
Multi-step reaction with 3 steps 1: -78 °C 2: lithium 2,2,6,6-tetramethylpiperidide / tetrahydrofuran; diethyl ether / 1 h / -107 °C 3: 50 percent / (Cl2CBr)2 / tetrahydrofuran; diethyl ether / -107 °C View Scheme

4-tert-butylpyridine N-oxide (23569-17-7) → 2-bromo-4-(tert-butyl)pyridine (50488-34-1)

Conditions	Yield
Stage #1: 4-tert-butylpyridine N-oxide With phosphorus(V) oxybromide In 1,2-dichloro-ethane at 20 - 70℃; Stage #2: With water; sodium hydroxide In 1,2-dichloro-ethane pH=10; Cooling;	14%
Multi-step reaction with 2 steps 1: trichlorophosphate / 24 h / Reflux 2: trimethylsilyl bromide / 48 h / Reflux View Scheme
Multi-step reaction with 2 steps 1: trichlorophosphate / 20 h / Cooling with ice; Reflux 2: trimethylsilyl bromide; propiononitrile / 21 h / Reflux View Scheme

C12H13F6NO (87432-73-3) → 2-bromo-4-(tert-butyl)pyridine (50488-34-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: lithium 2,2,6,6-tetramethylpiperidide / tetrahydrofuran; diethyl ether / 1 h / -107 °C 2: 50 percent / (Cl2CBr)2 / tetrahydrofuran; diethyl ether / -107 °C View Scheme

2-bromo-9H-carbazole (3652-90-2) + 2-bromo-4-(tert-butyl)pyridine (50488-34-1) → 2-bromo-9-(4-(tert-butyl)pyridin-2-yl)-9H-carbazole

Conditions	Yield
With 1-methyl-1H-imidazole; copper(l) iodide; lithium tert-butoxide In toluene at 130℃; for 24h; Inert atmosphere;	99%
With 1-methyl-1H-imidazole; copper(l) iodide; lithium tert-butoxide In toluene at 130℃; for 24h; Inert atmosphere;	99%
With 1-methyl-1H-imidazole; copper(l) iodide; lithium tert-butoxide In toluene at 20 - 130℃; for 48h; Inert atmosphere;	99%
With 1-methyl-1H-imidazole; copper(l) iodide; potassium carbonate In toluene at 115 - 125℃; for 96h; Inert atmosphere;	96%
With copper(l) iodide; potassium carbonate In toluene at 115 - 125℃; for 96h; Inert atmosphere;	96%

6-bromo-2-methoxy-9H-carbazole + 2-bromo-4-(tert-butyl)pyridine (50488-34-1) → C22H21BrN2O

Conditions	Yield
With potassium phosphate; copper(l) iodide; trans-1,2-cyclohexanediamine In 1,4-dioxane at 120℃; for 12h;	95%

2-(3-(3,5-dimethyl-1H-pyrazol-1-yl)phenoxy)-9H-carbazole (1393812-51-5) + 2-bromo-4-(tert-butyl)pyridine (50488-34-1) → 2-(3-(3,5-dimethyl-1H-pyrazol-1-yl)phenoxy)-9-(4-tert-butylpyridin-2-yl)-9H-carbazole

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); johnphos; sodium t-butanolate In 1,4-dioxane; toluene at 95 - 105℃; for 48h; Inert atmosphere;	94%
With tris-(dibenzylideneacetone)dipalladium(0); johnphos; sodium t-butanolate In 1,4-dioxane; toluene at 95 - 105℃; for 48h; Schlenk technique; Inert atmosphere; Sealed tube;	94%

6-tert-butyl-2-methoxycarbazole + 2-bromo-4-(tert-butyl)pyridine (50488-34-1) → C26H30N2O

Conditions	Yield
With 1-methyl-1H-imidazole; copper(l) chloride; lithium tert-butoxide In toluene at 130℃; for 42h; Inert atmosphere;	93%

3-methoxy-N-phenylaniline (101-16-6) + 2-bromo-4-(tert-butyl)pyridine (50488-34-1) → 4-(tert-butyl)-N-(3-methoxyphenyl)-N-phenylpyridin-2-amine

Conditions	Yield
With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate In toluene for 18h; Reflux;	89%

2'-(1H-pyrazol-1-yl)-9H-2,9'-bicarbazole + 2-bromo-4-(tert-butyl)pyridine (50488-34-1) → 9-(4-tert-butylpyridin-2-yl)-2'-(1H-pyrazol-1-yl)-9H-2,9'-bicarbazole

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); johnphos; sodium t-butanolate In 1,4-dioxane; toluene at 95 - 105℃; for 48h; Inert atmosphere;	88%

2-(3-(4-phenyl-1H-pyrazol-1-yl)phenoxy)-9H-carbazole + 2-bromo-4-(tert-butyl)pyridine (50488-34-1) → 9-(4-tert-butylpyridin-2-yl)-2-(3-(4-phenyl-1H-pyrazol-1-yl)phenoxy)-9H-carbazole

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); johnphos; sodium t-butanolate In 1,4-dioxane; toluene at 100 - 110℃; for 39h; Inert atmosphere; Sealed tube;	86%
With tris-(dibenzylideneacetone)dipalladium(0); johnphos In 1,4-dioxane; toluene at 100 - 110℃; for 39h; Schlenk technique; Inert atmosphere; Sealed tube;

2-methoxy-9H-carbazole (6933-49-9) + 2-bromo-4-(tert-butyl)pyridine (50488-34-1) → C22H22N2O

Conditions	Yield
With potassium phosphate; copper(l) iodide; trans-1,2-cyclohexanediamine In 1,4-dioxane at 120℃; for 12h;	85%
With potassium phosphate; copper(l) iodide; rac-diaminocyclohexane In 1,4-dioxane at 120℃; for 18h;	80%

2-methoxy-6-methyl-(9H)-carbazole (32550-53-1) + 2-bromo-4-(tert-butyl)pyridine (50488-34-1) → C23H24N2O

Conditions	Yield
With 1-methyl-1H-imidazole; copper(l) chloride; lithium tert-butoxide In toluene at 130℃; for 24h; Inert atmosphere;	80%

2-amino-N-(2-(2-methyl-1H-indol-3-yl)ethyl)pyrimidine-5-carboxamide + 2-bromo-4-(tert-butyl)pyridine (50488-34-1) → 2-((4-(tert-butyl)pyridin-2-yl)amino)-N-(2-(2-methyl-1H-indol-3-yl)ethyl)pyrimidine-5-carboxamide

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene In 1,4-dioxane at 100℃; Inert atmosphere;	80%

tert-butyl (4S)-4-[(3Z)-3-tert-butylsulfinyliminopropyl]-2,2-dimethylpyrrolidine-1-carboxylate + 2-bromo-4-(tert-butyl)pyridine (50488-34-1) → tert-butyl (4S)-4-[3-(4-tert-butyl-2-pyridyl)-3-(tert-butylsulfinylamino)propyl]-2,2-dimethylpyrrolidine-1-carboxylate

Conditions	Yield
Stage #1: 4-(tert-butyl)-2-bromopyridine With n-butyllithium In diethyl ether; hexane at -70℃; for 0.666667h; Inert atmosphere; Stage #2: tert-butyl (4S)-4-[(3Z)-3-tert-butylsulfinyliminopropyl]-2,2-dimethylpyrrolidine-1-carboxylate In tetrahydrofuran; diethyl ether; hexane at -78 - -40℃; for 0.75h; Inert atmosphere;	79%

4-ethoxycarbonyl-2-(pyridin-2-yl)pyridine N-oxide (1286763-08-3) + 2-bromo-4-(tert-butyl)pyridine (50488-34-1) → 4-tert-butyl-4'-ethoxycarbonyl-2,2':6',2''-terpyridine N'-oxide

Conditions	Yield
With potassium phosphate; methyldi-t-butylphosphine; palladium diacetate In toluene at 120℃; for 24h; Inert atmosphere; Glovebox;	71%

4-ethoxycarbonyl-2-(4-methoxypyridin-2-yl)pyridine N-oxide (1286763-32-3) + 2-bromo-4-(tert-butyl)pyridine (50488-34-1) → 4''-(tert-butyl)-4'-ethoxycarbonyl-4-methoxy-2,2':6',2''-terpyridine N'-oxide

Conditions	Yield
With potassium phosphate; methyldi-t-butylphosphine; palladium diacetate In toluene at 120℃; for 24h; Inert atmosphere; Glovebox;	67%

4-ethoxycarbonyl-2-(6-methoxypyridin-2-yl)pyridine N-oxide (1286763-24-3) + 2-bromo-4-(tert-butyl)pyridine (50488-34-1) → 4''-(tert-butyl)-4'-ethoxycarbonyl-6-methoxy-2,2':6',2''-terpyridine N'-oxide

Conditions	Yield
With potassium phosphate; methyldi-t-butylphosphine; palladium diacetate In toluene at 120℃; for 24h; Inert atmosphere; Glovebox;	64%

2,2'-(oxybis(3,1-phenylene))bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) + 2-bromo-4-(tert-butyl)pyridine (50488-34-1) → C30H32N2O

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In ethanol; water at 80℃; for 24h;	64%

2-bromo-4-(tert-butyl)pyridine (50488-34-1) + 4-tert-butylphenylboronic acid (123324-71-0) → 4-(tert-butyl)-2-(4-(tert-butyl)phenyl)pyridine (808142-68-9)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); ethanol; sodium carbonate In benzene at 70℃; for 48h; Suzuki coupling;	61%

4'-tert-butyl-4-ethoxycarbonyl-2,2'-bipyridine N-oxide + 2-bromo-4-(tert-butyl)pyridine (50488-34-1) → 4,4''-bis(tert-butyl)-4'-ethoxycarbonyl-2,2':6′,2''-terpyridine N'-oxide

Conditions	Yield
With potassium phosphate; methyldi-t-butylphosphine; palladium diacetate In toluene at 120℃; for 24h; Inert atmosphere; Glovebox;	59%

C15H22BF3N2O3 + 2-bromo-4-(tert-butyl)pyridine (50488-34-1) → 4-(tert-butyl)-2-(3-(trifluoromethyl)-1H-pyrazol-5-yl)pyridine (1026999-80-3)

Conditions	Yield
Stage #1: C15H22BF3N2O3; 4-(tert-butyl)-2-bromopyridine With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water at 70℃; Stage #2: With hydrogenchloride In 1,4-dioxane; water at 60℃;	58%

1H-imidazole (288-32-4) + 2-bromo-4-(tert-butyl)pyridine (50488-34-1) → 4-tert-butyl-2-(1H-imidazol-1-yl)pyridine (1261616-69-6)

Conditions	Yield
With copper(l) iodide; potassium carbonate; L-proline In dimethyl sulfoxide at 75℃; for 47h; Ullmann coupling; Inert atmosphere;	57%

ethyl isonicotinate N-oxide (14906-37-7) + 2-bromo-4-(tert-butyl)pyridine (50488-34-1) → 4'-tert-butyl-4-ethoxycarbonyl-2,2'-bipyridine N-oxide + 4,4''-bis(tert-butyl)-4'-ethoxycarbonyl-2,2':6′,2''-terpyridine N'-oxide

Conditions	Yield
With potassium phosphate; tri-tert-butyl phosphine; palladium diacetate In toluene at 120℃; for 24h; Concentration; Inert atmosphere; Glovebox;	A 57% B 7%

tert-butyl (3R)-3-[(3E)-3-tert-butylsulfinyliminopropyl]piperidine-1-carboxylate + 2-bromo-4-(tert-butyl)pyridine (50488-34-1) → tert-butyl (3R)-3-[3-(4-tert-butyl-2-pyridyl)-3-(tert-butylsulfinylamino)propyl]piperidine-1-carboxylate

Conditions	Yield
Stage #1: 4-(tert-butyl)-2-bromopyridine With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.75h; Stage #2: tert-butyl (3R)-3-[(3E)-3-tert-butylsulfinyliminopropyl]piperidine-1-carboxylate In tetrahydrofuran; hexane at 20℃; for 4h;	57%

6-(methylsulfanyl)-2-(propan-2-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one (955368-93-1) + 2-bromo-4-(tert-butyl)pyridine (50488-34-1) → 1-(4-(tert-butyl)pyridin-2-yl)-2-isopropyl-6-(methylthio)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one

Conditions	Yield
With copper(l) iodide; potassium carbonate; N,N`-dimethylethylenediamine In 1,4-dioxane at 90℃;	56.5%

2-bromo-4-(tert-butyl)pyridine (50488-34-1) + phenylboronic acid (98-80-6) → 4-(tert-butyl)-2-phenylpyridine (53911-36-7)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In ethanol; water; toluene Inert atmosphere; Reflux;	55%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In ethanol; water; toluene at 70℃; for 16h; Inert atmosphere;

2-bromo-4-(tert-butyl)pyridine (50488-34-1) → 2-bromo-4-(tert-butyl)-6-fluoropyridine

Conditions	Yield
With silver(II) fluoride In acetonitrile at 20℃; Inert atmosphere; Autoclave;	51%

2,2'-(4,6-difluoro-1,3-phenylene)bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) (1136948-11-2) + 2-bromo-4-(tert-butyl)pyridine (50488-34-1) → 1,5-bis(4-tert-butylpyridine-2-yl)-2,4-difluorobenzene

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In 1,2-dimethoxyethane for 48h; Suzuki-Miyaura Coupling; Inert atmosphere; Reflux;	50%
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In 1,2-dimethoxyethane for 48h; Reflux;	50%

Upstream product

• 81167-60-4 2-chloro-4-(1,1-dimethylethyl)pyridine 
• 23569-17-7 4-tert-butylpyridine N-oxide 
• 3978-81-2 4-tert-butylpyridine 
• 87432-73-3 C₁₂H₁₃F₆NO 

Downstream Products

• 42205-74-3 4-tert-Butylpyridine-2-carboxylic acid 
• 583052-24-8 2-(2',4'-difluorophenyl)-4-tert-butyl-pyridine 
• 53911-36-7 4-(tert-butyl)-2-phenylpyridine 
• 1261616-77-6 4-tert-butyl-2-(4-phenyl-1H-imidazol-1-yl)-pyridine 
• 808142-68-9 4-(tert-butyl)-2-(4-(tert-butyl)phenyl)pyridine 

Relevant articles and documents

MODULATORS OF CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR

This disclosure provides modulators of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), pharmaceutical compositions containing at least one such modulator, methods of treatment of cystic fibrosis using such modulators and pharmaceutical compositions, and processes for making such modulators.

ORGANIC ELECTROLUMINESCENT MATERIALS AND DEVICES

A compound including a ligand L according to formula I, a first device and a formulation containing the same are disclosed. In the compound including the ligand L of formula I, R^1 and R^2 are independently selected from group consisting of hydrogen, deuterium, halide, alkyl, cycloalkyl, heteroalkyl, arylalkyl, alkoxy, aryloxy, amino, silyl, alkenyl, cycloalkenyl, heteroalkenyl, alkynyl, aryl, heteroaryl, acyl, carbonyl, carboxylic acids, ester, nitrile, isonitrile, sulfanyl, sulfinyl, sulfonyl, phosphino, cyano, and combinations thereof; two adjacent substituents of R^1 or R^2 are optionally joined to form a fused ring; a ligand L is coordinated to transition metal M having an atomic number greater than 40; R^1 represents mono, di, tri, or tetra-substitution, or no substitution; R^2 represents mono, di, or tri-substitution, or no substitution; and at least one substituent of R^1 or R^2 is cyano.COPYRIGHT KIPO 2015

A simple synthesis of functionalized 3-methyl-1-pyridinyl-1H-imidazolium salts as bidentate N-heterocyclic-carbene precursors and their application in Ir-catalyzed arene borylation

The selective alkylation of functionalized 2-(1H-imidazol-1-yl)pyridines 1 furnishes 3-methyl-1-pyridinyl-1H-imidazolium salts 2, which can be deprotonated to deliver strongly electron-donating bidentate N-heterocyclic carbene ligands (NHC). The synthesis of these ligands and their application in the iridiumcatalyzed C-H activated borylation of arenes with its current scope and limitations are reported.