156682-53-0

Basic information

• Product Name: 3-Bromo-2-fluoro-phenol
• Synonyms: 3-Bromo-2-fluoro-phenol;3-Bromo-2-fluorophenol98%
• CAS NO: 156682-53-0
• Molecular Formula: C₆H₄BrFO
• Molecular Weight: 190.9977632
• Mol File: 156682-53-0.mol
• Article Data: 2

Chemical Properties

• Boiling Point: 207.4 °C at 760 mmHg
• Flash Point: 79.2 °C
• Appearance: /
• Density: 1.764 g/cm³
• Vapor Pressure: 0.157mmHg at 25°C
• Refractive Index: 1.575
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 7.74±0.10(Predicted)
• CAS DataBase Reference: 3-Bromo-2-fluoro-phenol(CAS DataBase Reference)
• NIST Chemistry Reference: 3-Bromo-2-fluoro-phenol(156682-53-0)
• EPA Substance Registry System: 3-Bromo-2-fluoro-phenol(156682-53-0)

Safety Data

• Hazard Codes: T,Xi
• HazardClass: IRRITANT
• Hazardous Substances Data: 156682-53-0(Hazardous Substances Data)

Usage

General Description

3-Bromo-2-fluoro-phenol is a chemical compound with the molecular formula C6H4BrFO. It is a white to off-white solid at room temperature and is primarily used as a building block in the synthesis of various pharmaceuticals and agrochemicals. 3-Bromo-2-fluoro-phenol is also utilized in the manufacturing of specialty chemicals and as an intermediate in organic synthesis. 3-Bromo-2-fluoro-phenol is known for its reactivity and is handled and stored with care due to its potential hazards. It is important to follow proper safety protocols when handling and working with this chemical.

InChI:InChI=1/C6H4BrFO/c7-4-2-1-3-5(9)6(4)8/h1-3,9H

Synthetic route

1-bromo-2,3-difluorobenzene (38573-88-5) → 3-bromo-2-fluoro-phenol (156682-53-0) + 2-bromo-6-fluorophenol (2040-89-3)

Conditions	Yield
Stage #1: 1-bromo-2,3-difluorobenzene With potassium trimethylsilonate In diethylene glycol dimethyl ether at 120℃; for 5h; Inert atmosphere; Stage #2: With hydrogenchloride In diethylene glycol dimethyl ether; water at 20℃; Inert atmosphere;

3-bromo-2-fluoro-phenol (156682-53-0) + benzyl bromide (100-39-0) → 1-(benzyloxy)-3-bromo-2-fluorobenzene (295376-29-3)

Conditions	Yield
With potassium carbonate In acetone for 4h; Reflux;	97%

3-bromo-2-fluoro-phenol (156682-53-0) + 6-(benzyloxy)-4-chloro-7-methoxyquinazoline (286371-65-1) → 6-benzyloxy-4-(3-bromo-2-fluorophenoxy)-7-methoxyquinazoline

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 90℃; for 1h;	96%

3-bromo-2-fluoro-phenol (156682-53-0) + isopropyl bromide (75-26-3) → 1-bromo-2-fluoro-3-isopropoxybenzene (1160293-59-3)

Conditions	Yield
With potassium carbonate In acetone at 60℃; for 14h; Inert atmosphere;	92%

3-bromo-2-fluoro-phenol (156682-53-0) + cyclohexylmethyl alcohol (100-49-2) → 1-bromo-3-(cyclohexylmethoxy)-2-fluorobenzene

Conditions	Yield
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 20℃; for 16h;	83%

3-bromo-2-fluoro-phenol (156682-53-0) + 6,7-dibenzyloxy-4-chloroquinazoline → 6,7-dibenzyloxy-4-(3-bromo-2-fluorophenoxy)quinazoline

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 1h;	82%

3-bromo-2-fluoro-phenol (156682-53-0) + benzyl (3S)-3-((4-(2-fluoro-3-pyridyl)pyrimidin-2-yl)amino)piperidine-1-carboxylate → benzyl (3S)-3-((4-(2-(3-bromo-2-fluoro-phenoxy)-3-pyridyl)pyrimidin-2-yl)amino)piperidine-1-carboxylate

Conditions	Yield
With caesium carbonate In dimethyl sulfoxide at 110℃; for 1h;	76.8%

3-bromo-2-fluoro-phenol (156682-53-0) + diphenyliodonium tetrafluoroborate → 1-bromo-2-fluoro-3-phenoxybenzene

Conditions	Yield
Stage #1: 3-bromo-2-fluoro-phenol With potassium tert-butylate In tetrahydrofuran at 0℃; for 0.25h; Stage #2: diphenyliodonium tetrafluoroborate In tetrahydrofuran at 40℃; for 1h;	76%
Stage #1: 3-bromo-2-fluoro-phenol With potassium tert-butylate In tetrahydrofuran at 0℃; for 0.25h; Stage #2: diphenyliodonium tetrafluoroborate In tetrahydrofuran at 40℃; for 1h;	76%

3-bromo-2-fluoro-phenol (156682-53-0) + bis(3-fluorophenyl)iodonium tetrafluoroborate (1426251-76-4) → 1-bromo-2-fluoro-3-(3-fluorophenoxy)benzene

Conditions	Yield
Stage #1: 3-bromo-2-fluoro-phenol With potassium tert-butylate In tetrahydrofuran at 0℃; for 0.25h; Stage #2: bis(3-fluorophenyl)iodonium tetrafluoroborate In tetrahydrofuran at 40℃; for 1h;	71%
Stage #1: 3-bromo-2-fluoro-phenol With potassium tert-butylate In tetrahydrofuran at 0℃; for 0.25h; Stage #2: bis(3-fluorophenyl)iodonium tetrafluoroborate In tetrahydrofuran at 40℃; for 1h;	71%

3-bromo-2-fluoro-phenol (156682-53-0) + 2-methyl-3-bromo-1-propene (1458-98-6) → C10H10BrFO

Conditions	Yield
With potassium carbonate In acetonitrile for 18h; Inert atmosphere; Reflux;	70%

3-bromo-2-fluoro-phenol (156682-53-0) + sodium chlorodifluoroacetate (1895-39-2) → 1-bromo-3-(difluoromethoxy)-2-fluorobenzene (1242249-28-0)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 2h;	47%
With caesium carbonate In N,N-dimethyl-formamide at 100℃; for 2h;
With caesium carbonate In N,N-dimethyl-formamide at 100℃; for 4h;

4-bromotetrahydro-2H-pyran (25637-16-5) + 3-bromo-2-fluoro-phenol (156682-53-0) → C11H12BrFO2

Conditions	Yield
With caesium carbonate In acetonitrile at 80℃; for 18h;	31.24%

3-bromo-2-fluoro-phenol (156682-53-0) + (3-(aminocarbonyl)phenyl)boronic acid → 3-(2-fluoro-3-hydroxy-phenyl)benzamide

Conditions	Yield
With potassium phosphate; palladium bis[bis(diphenylphosphino)ferrocene] dichloride In 1,4-dioxane; ethanol at 100℃; for 1h; Inert atmosphere; Microwave irradiation; Sealed tube;	29%

3-bromo-2-fluoro-phenol (156682-53-0) + phenylboronic acid (98-80-6) → 1-bromo-2-fluoro-3-phenoxybenzene

Conditions	Yield
With copper diacetate; triethylamine In dichloromethane at 20℃; Molecular sieve;	4%

3-bromo-2-fluoro-phenol (156682-53-0) + 1-bromo-hexane (111-25-1) → 6-bromo-2-hexyloxyfluorobenzene (176317-01-4) + 2-Hexyloxy-1,6,7,8-tetrafluorophenanthrene

Conditions	Yield
With hydrogenchloride; potassium carbonate In water; acetone

3-bromo-2-fluoro-phenol (156682-53-0) → 2-(3-(difluoromethoxy)-2-fluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1313426-18-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: caesium carbonate / N,N-dimethyl-formamide / 2 h / 100 °C 2: potassium acetate / 1,4-dioxane / 2 h / 110 °C View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 100 °C 2: potassium acetate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,4-dioxane / 3 h / 110 °C View Scheme

3-bromo-2-fluoro-phenol (156682-53-0) → 4-[2-(benzyloxy)-6-bromophenoxymethyl]pyridine (1372147-59-5)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: potassium carbonate / acetone / 4 h / Reflux 2.1: sodium hydride / 1-methyl-pyrrolidin-2-one; mineral oil / 0.5 h / 60 °C / Cooling with ice 2.2: 2 h / 100 °C View Scheme

3-bromo-2-fluoro-phenol (156682-53-0) → 1-benzyl-4-[2-(benzyloxy)-6-bromophenoxymethyl]pyridinium bromide (1372147-65-3)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: potassium carbonate / acetone / 4 h / Reflux 2.1: sodium hydride / 1-methyl-pyrrolidin-2-one; mineral oil / 0.5 h / 60 °C / Cooling with ice 2.2: 2 h / 100 °C 3.1: acetone / 18 h / Reflux View Scheme

3-bromo-2-fluoro-phenol (156682-53-0) → 1-benzyl-4-[2-(benzyloxy)-6-bromophenoxymethyl]-1,2,3,6-tetrahydropyridine (1372147-73-3)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: potassium carbonate / acetone / 4 h / Reflux 2.1: sodium hydride / 1-methyl-pyrrolidin-2-one; mineral oil / 0.5 h / 60 °C / Cooling with ice 2.2: 2 h / 100 °C 3.1: acetone / 18 h / Reflux 4.1: sodium tetrahydroborate / methanol / 2 h / -5 - 20 °C View Scheme

3-bromo-2-fluoro-phenol (156682-53-0) → benzyl 4-[2-(benzyloxy)-6-bromophenoxymethyl]-1,2,3,6-tetrahydropyridine-1-carboxylate (1372147-81-3)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: potassium carbonate / acetone / 4 h / Reflux 2.1: sodium hydride / 1-methyl-pyrrolidin-2-one; mineral oil / 0.5 h / 60 °C / Cooling with ice 2.2: 2 h / 100 °C 3.1: acetone / 18 h / Reflux 4.1: sodium tetrahydroborate / methanol / 2 h / -5 - 20 °C 5.1: potassium hydrogencarbonate / dichloromethane / 24 h / 0 - 20 °C View Scheme

3-bromo-2-fluoro-phenol (156682-53-0) → ethyl 4-[2-(benzyloxy)-6-bromophenoxymethyl]-1,2,3,6-tetrahydropyridine-1-carboxylate (1372147-83-5)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: potassium carbonate / acetone / 4 h / Reflux 2.1: sodium hydride / 1-methyl-pyrrolidin-2-one; mineral oil / 0.5 h / 60 °C / Cooling with ice 2.2: 2 h / 100 °C 3.1: acetone / 18 h / Reflux 4.1: sodium tetrahydroborate / methanol / 2 h / -5 - 20 °C 5.1: potassium hydrogencarbonate / 1,2-dichloro-ethane / 2 h / Reflux View Scheme

3-bromo-2-fluoro-phenol (156682-53-0) → benzyl 7-(benzyloxy)-2',3'-dihydro-1'H,2H-spiro[1-benzofuran-3,4'-pyridine]-1'-carboxylate (1372147-92-6)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: potassium carbonate / acetone / 4 h / Reflux 2.1: sodium hydride / 1-methyl-pyrrolidin-2-one; mineral oil / 0.5 h / 60 °C / Cooling with ice 2.2: 2 h / 100 °C 3.1: acetone / 18 h / Reflux 4.1: sodium tetrahydroborate / methanol / 2 h / -5 - 20 °C 5.1: potassium hydrogencarbonate / dichloromethane / 24 h / 0 - 20 °C 6.1: trans-di(μ-acetato)bis[o-(di-o-tolylphosphino)benzyl]dipalladium(II); silver carbonate / 1-methyl-pyrrolidin-2-one / 18 h / 140 °C / Inert atmosphere View Scheme

3-bromo-2-fluoro-phenol (156682-53-0) → ethyl 7-(benzyloxy)-2',3'-dihydro-1'H,2H-spiro[1-benzofuran-3,4'-pyridine]-1'-carboxylate (1372147-94-8)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: potassium carbonate / acetone / 4 h / Reflux 2.1: sodium hydride / 1-methyl-pyrrolidin-2-one; mineral oil / 0.5 h / 60 °C / Cooling with ice 2.2: 2 h / 100 °C 3.1: acetone / 18 h / Reflux 4.1: sodium tetrahydroborate / methanol / 2 h / -5 - 20 °C 5.1: potassium hydrogencarbonate / 1,2-dichloro-ethane / 2 h / Reflux 6.1: trans-di(μ-acetato)bis[o-(di-o-tolylphosphino)benzyl]dipalladium(II); silver carbonate / 1-methyl-pyrrolidin-2-one / 18 h / 140 °C / Inert atmosphere View Scheme

3-bromo-2-fluoro-phenol (156682-53-0) → ethyl 7-hydroxy-2H-spiro[1-benzofuran-3,4'-piperidine]-1'-carboxylate (1372148-02-1)

Conditions

Yield

Multi-step reaction with 7 steps 1.1: potassium carbonate / acetone / 4 h / Reflux 2.1: sodium hydride / 1-methyl-pyrrolidin-2-one; mineral oil / 0.5 h / 60 °C / Cooling with ice 2.2: 2 h / 100 °C 3.1: acetone / 18 h / Reflux 4.1: sodium tetrahydroborate / methanol / 2 h / -5 - 20 °C 5.1: potassium hydrogencarbonate / 1,2-dichloro-ethane / 2 h / Reflux 6.1: trans-di(μ-acetato)bis[o-(di-o-tolylphosphino)benzyl]dipalladium(II); silver carbonate / 1-methyl-pyrrolidin-2-one / 18 h / 140 °C / Inert atmosphere 7.1: palladium 10% on activated carbon; hydrogen / methanol; ethyl acetate / 18 h / 20 °C / 760.05 Torr View Scheme

3-bromo-2-fluoro-phenol (156682-53-0) → 2H-spiro[1-benzofuran-3,4'-piperidin]-7-ol hydrochloride (1372148-00-9)

Conditions

Yield

Multi-step reaction with 8 steps 1.1: potassium carbonate / acetone / 4 h / Reflux 2.1: sodium hydride / 1-methyl-pyrrolidin-2-one; mineral oil / 0.5 h / 60 °C / Cooling with ice 2.2: 2 h / 100 °C 3.1: acetone / 18 h / Reflux 4.1: sodium tetrahydroborate / methanol / 2 h / -5 - 20 °C 5.1: potassium hydrogencarbonate / 1,2-dichloro-ethane / 2 h / Reflux 6.1: trans-di(μ-acetato)bis[o-(di-o-tolylphosphino)benzyl]dipalladium(II); silver carbonate / 1-methyl-pyrrolidin-2-one / 18 h / 140 °C / Inert atmosphere 7.1: palladium 10% on activated carbon; hydrogen / methanol; ethyl acetate / 18 h / 20 °C / 760.05 Torr 8.1: hydrogenchloride; water; acetic acid / 18 h / Reflux View Scheme

tetrahydrofurfuryl bromide (1192-30-9) + 3-bromo-2-fluoro-phenol (156682-53-0) → 2-(3-bromo-2-fluoro-phenoxymethyl)-tetrahydrofuran (1398923-65-3)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 130℃; for 2h; Inert atmosphere;

3-bromo-2-fluoro-phenol (156682-53-0) → cis-7-[3-(1,1-dioxo-1-thiomorpholin-4-ylmethyl)-cyclobutyl]-5-[2-fluoro-3-(tetrahydro-furan-2-ylmethoxy)-phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine

Conditions

Yield

Multi-step reaction with 3 steps 1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 130 °C / Inert atmosphere 2: potassium acetate / dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / N,N-dimethyl-formamide / 18 h / 80 °C / Inert atmosphere 3: potassium phosphate; sodium carbonate / tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide; water / 1.5 h / 100 °C / Inert atmosphere; sealed tube View Scheme

3-bromo-2-fluoro-phenol (156682-53-0) → 2-(4-amino-5-{2-fluoro-3-[(S)-1-(tetrahydro-furan-2-yl)methoxy]-phenyl}-pyrrolo[2,3-d]pyrimidin-7-yl)-5-oxa-7-aza-spiro[3.4]octan-6-one

Conditions

Yield

Multi-step reaction with 3 steps 1: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 18 h / 20 °C 2: potassium acetate / dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / N,N-dimethyl-formamide / 18 h / 100 °C / Inert atmosphere 3: potassium phosphate; sodium carbonate / tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide; water / 1.5 h / 80 °C / Inert atmosphere; sealed tube View Scheme

3-bromo-2-fluoro-phenol (156682-53-0) → 1-{4-[cis-3-(4-amino-5-{2-fluoro-3-[(S)-1-(tetrahydro-furan-2-yl)methoxy]-phenyl}-pyrrolo[2,3-d]pyrimidin-7-yl)-cyclobutyl]-piperazin-1-yl}-ethanone

Conditions

Yield

Multi-step reaction with 3 steps 1: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 18 h / 20 °C 2: potassium acetate / dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / N,N-dimethyl-formamide / 18 h / 100 °C / Inert atmosphere 3: potassium phosphate; sodium carbonate / tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide; water / 2.5 h / 100 °C / Inert atmosphere; sealed tube View Scheme

Upstream product

• 38573-88-5 1-bromo-2,3-difluorobenzene 

Downstream Products

• 176317-01-4 6-bromo-2-hexyloxyfluorobenzene 
• 1398923-81-3 d9-1-[2-fluoro-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenoxymethyl]-7-oxa-bicyclo[2.2.1]heptane 
• 1398923-83-5 d9-1-(3-bromo-2-fluoro-phenoxymethyl)-7-oxa-bicyclo[2.2.1]heptane 
• 1398923-73-3 1-[2-fluoro-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenoxymethyl]-7-oxa-bicyclo[2.2.1]heptane 
• 1398923-75-5 1-(3-bromo-2-fluoro-phenoxymethyl)-7-oxa-bicyclo[2.2.1]heptane 
• 1398923-71-1 (S)-2-(3-bromo-2-fluoro-phenoxymethyl)-tetrahydrofuran 
• 1398923-69-7 2-{2-fluoro-3-[(S)-1-(tetrahydro-furan-2-yl)methoxy]-phenyl}-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane 
• 1398923-63-1 2-[2-fluoro-3-(tetrahydro-furan-2-ylmethoxy)-phenyl]-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane 
• 1398923-65-3 2-(3-bromo-2-fluoro-phenoxymethyl)-tetrahydrofuran 

Relevant articles and documents

Preparation of monofluorophenols via the reaction of difluorobenzene derivatives with potassium trimethylsilanoate

An efficient synthesis of monofluorophenols via the reaction of difluorobenzene derivatives with potassium trimethylsilanoate in moderate to excellent yields is described. High regioselectivity was observed in some cases. Georg Thieme Verlag Stuttgart.