32454-35-6

Basic information

• Product Name: 2-(4-Bromophenyl)-2-methylpropionic acid
• Synonyms: 2-(4-Bromophenyl)(dimethyl)acetic acid, 2-(4-Bromophenyl)-2-methylpropionic acid;2-(4-Bromophenyl)-2-methylpropionic acid-3;2-(4-BROMOPHENYL)-2-METHYLPROPIONIC ACID;2-METHYL-2-(4-BROMOPHENYL) PROPIONIC ACID;2-Methyl-2-(P-Bromophenyl)Propionic Acid;2-Methyl-2-(p-bromphenyl)propionic acid;4-Bromo-alpha,alpha-dimethylphenylacetic acid;P-Bromo a,a-Dimethyl Phenyl Acetic Acid
• CAS NO: 32454-35-6
• Molecular Formula: C₁₀H₁₁BrO₂
• Molecular Weight: 243.1
• EINECS: 1312995-182-4
• Product Categories: Aromatics
• Mol File: 32454-35-6.mol
• Article Data: 18

Chemical Properties

• Melting Point: 122-124°C
• Boiling Point: 334.239 °C at 760 mmHg
• Flash Point: 155.942 °C
• Appearance: White Solid
• Density: 1.456 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.559
• Storage Temp.: Room temperature.
• Solubility: Dichloromethane, Ethyl Acetate, Methanol
• PKA: 4.26±0.10(Predicted)
• CAS DataBase Reference: 2-(4-Bromophenyl)-2-methylpropionic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 2-(4-Bromophenyl)-2-methylpropionic acid(32454-35-6)
• EPA Substance Registry System: 2-(4-Bromophenyl)-2-methylpropionic acid(32454-35-6)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• Hazardous Substances Data: 32454-35-6(Hazardous Substances Data)

Usage

Chemical Properties

White Solid

InChI:InChI=1/C10H11BrO2/c1-10(2,9(12)13)7-3-5-8(11)6-4-7/h3-6H,1-2H3,(H,12,13)

Synthetic route

2-(4-bromophenyl)-2-methylpropanenitrile (101184-73-0) → 2-(4-bromophenyl)-2-methylpropionic acid (32454-35-6)

Conditions	Yield
With potassium hydroxide In ethanol; water at 80 - 85℃; for 18h; Hydrolysis;	99%
With water; potassium hydroxide In ethanol for 20h; Reflux;	5.3 g
With potassium hydroxide In ethylene glycol for 4h; Reflux;

1-bromo-4-(2-isocyanopropan-2-yl)benzene → 2-(4-bromophenyl)-2-methylpropionic acid (32454-35-6)

Conditions	Yield
With water; sodium hydroxide In ethanol at 100℃; for 16h;	99%

methyl 2-(4-bromophenyl)-2,2-dimethylacetate (154825-97-5) → 2-(4-bromophenyl)-2-methylpropionic acid (32454-35-6)

Conditions	Yield
Stage #1: methyl 2-(4-bromophenyl)-2,2-dimethylacetate With water; lithium hydroxide In 1,4-dioxane at 50℃; for 5.5h; Stage #2: With hydrogenchloride In 1,4-dioxane; water	94%
Stage #1: methyl 2-(4-bromophenyl)-2,2-dimethylacetate With methanol; lithium hydroxide; water In tetrahydrofuran at 0 - 20℃; for 3h; Stage #2: With hydrogenchloride In water at 0℃;
Stage #1: methyl 2-(4-bromophenyl)-2,2-dimethylacetate With potassium hydroxide; ethanol; water at 90℃; for 15h; Stage #2: With hydrogenchloride; water pH=2.0;

C15H20BrClO2 → 2-(4-bromophenyl)-2-methylpropionic acid (32454-35-6)

Conditions	Yield
With water; sodium hydroxide In methanol for 2h; Reflux;	86%

2-methyl-2-phenylpropionic acid (826-55-1) → 2-(4-bromophenyl)-2-methylpropionic acid (32454-35-6)

Conditions	Yield
Stage #1: 2-methyl-2-phenylpropionic acid With bromine; sodium carbonate In water at 25 - 30℃; pH=7; Stage #2: With hydrogenchloride In water pH=1 - 2; Product distribution / selectivity;	81%
Stage #1: 2-methyl-2-phenylpropionic acid With bromine; sodium hydrogencarbonate In water at 25 - 35℃; for 13h; Industry scale; Stage #2: With hydrogenchloride In water at 0 - 10℃; pH=5; Product distribution / selectivity;	46.6%
With tetrachloromethane; bromine; iron

Ethyl 4-bromophenylacetate (14062-25-0) + methyl iodide (74-88-4) → 2-(4-bromophenyl)-2-methylpropionic acid (32454-35-6)

Conditions	Yield
With sodium hydride

2-(4-bromophenyl)-2-methyl-propionic acid ethyl ester (32454-36-7) → 2-(4-bromophenyl)-2-methylpropionic acid (32454-35-6)

Conditions	Yield
With methanol; sodium hydroxide; water In tetrahydrofuran at 20℃; for 16h;
Stage #1: 2-(4-bromophenyl)-2-methyl-propionic acid ethyl ester With methanol; potassium hydroxide; water at 0℃; for 2h; Heating / reflux; Stage #2: With hydrogenchloride; methanol In water

potassium trimethylsilonate (10519-96-7) + methyl 2-(4-bromophenyl)-2,2-dimethylacetate (154825-97-5) → 2-(4-bromophenyl)-2-methylpropionic acid (32454-35-6)

Conditions	Yield
With hydrogenchloride In tetrahydrofuran

benzene (71-43-2) → 2-(4-bromophenyl)-2-methylpropionic acid (32454-35-6)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: aluminum (III) chloride / Industry scale 2.1: sodium hydrogencarbonate; bromine / water / 13 h / 25 - 35 °C / Industry scale 2.2: 0 - 10 °C / pH 5 View Scheme
Multi-step reaction with 2 steps 1.1: aluminum (III) chloride / Industry scale 2.1: bromine; sodium carbonate / water / 25 - 30 °C / pH 7 2.2: pH 1 - 2 View Scheme

2-(4-bromophenyl)propionic acid (53086-53-6) + methyl iodide (74-88-4) → 2-(4-bromophenyl)-2-methylpropionic acid (32454-35-6)

Conditions	Yield
Stage #1: 2-(4-bromophenyl)propionic acid With lithium diisopropyl amide In tetrahydrofuran at 45℃; for 1h; Inert atmosphere; Cooling with ice; Stage #2: methyl iodide In tetrahydrofuran at 0 - 20℃; Inert atmosphere;

(4-bromo-phenyl)-acetic acid methyl ester (41841-16-1) + methyl iodide (74-88-4) → 2-(4-bromophenyl)-2-methylpropionic acid (32454-35-6)

Conditions	Yield
Stage #1: (4-bromo-phenyl)-acetic acid methyl ester; methyl iodide With sodium hydride Stage #2: With potassium hydroxide

2-(4-bromophenyl)-2-methylpropionic acid (32454-35-6) → 2,2-dimethyl-2-(4-bromophenyl)ethanol (32454-37-8)

Conditions	Yield
Stage #1: 2-(4-bromophenyl)-2-methylpropionic acid With borane-THF In tetrahydrofuran at 0 - 20℃; Stage #2: With hydrogenchloride In tetrahydrofuran; water	100%
With lithium aluminium tetrahydride; diethyl ether
With lithium aluminium tetrahydride In diethyl ether at -78 - 23℃;
With lithium aluminium tetrahydride In diethyl ether at 20℃; Inert atmosphere;

methanol (67-56-1) + 2-(4-bromophenyl)-2-methylpropionic acid (32454-35-6) → methyl 2-(4-bromophenyl)-2,2-dimethylacetate (154825-97-5)

Conditions	Yield
With sulfuric acid; acetonitrile at 80 - 85℃; for 16 - 18h;	98%
With sulfuric acid In toluene at 63 - 67℃; for 16h; Industry scale;	79%
With sulfuric acid In toluene at 63 - 67℃; for 16h; Industry scale;	79%

tert-butyl methyl ether (1634-04-4) + 2-(4-bromophenyl)-2-methylpropionic acid (32454-35-6) → methyl 2-(4-bromophenyl)-2,2-dimethylacetate (154825-97-5)

Conditions	Yield
With sulfuric acid Reflux; regioselective reaction;	93%

2-(4-bromophenyl)-2-methylpropionic acid (32454-35-6) + benzyl alcohol (100-51-6) → benzyl N-[1-(4-bromophenyl)-1-methylethyl]carbamate (578729-08-5)

Conditions	Yield
Stage #1: 2-(4-bromophenyl)-2-methylpropionic acid With diphenyl phosphoryl azide; triethylamine In toluene for 4h; Reflux; Stage #2: benzyl alcohol In toluene Reflux;	69%

2-(4-bromophenyl)-2-methylpropionic acid (32454-35-6) → 2-(4-bromophenyl)propan-2-ol (2077-19-2)

Conditions	Yield
With 2,4,6-trimethyl-pyridine; water; tert-butylammonium hexafluorophosphate(V) In acetone at 20℃; for 3h; Electrolysis;	67%

2-(4-bromophenyl)-2-methylpropionic acid (32454-35-6) + 3-[3-(4-fluoro-phenyl)-1-isopropyl-2,3-dihydro-1H-indol-2-yl]-propenal → 2-(4-{3-[3-(4-fluoro-phenyl)-1-isopropyl-2,3-dihydro-1H-indol-2-yl]-1-hydroxy-allyl}-phenyl)-2-methyl-propionic acid

Conditions	Yield
Stage #1: 2-(4-bromophenyl)-2-methylpropionic acid With sodium hydride In tetrahydrofuran deprotonation; Stage #2: With tert.-butyl lithium In tetrahydrofuran at -72℃; Metallation; Stage #3: 3-[3-(4-fluoro-phenyl)-1-isopropyl-2,3-dihydro-1H-indol-2-yl]-propenal In tetrahydrofuran at -72℃; Condensation;	65%

2-(4-bromophenyl)-2-methylpropionic acid (32454-35-6) + bis(pinacol)diborane (73183-34-3) → 2-methyl-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propanoic acid (909187-36-6)

Conditions	Yield
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate In dimethyl sulfoxide at 80℃; Inert atmosphere;	63%
With potassium acetate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 In 1,4-dioxane; water at 80℃; for 18h;

2-(4-bromophenyl)-2-methylpropionic acid (32454-35-6) → 6-bromo-3,3-dimethylbenzofuran-2(3H)-one (1418028-03-1)

Conditions	Yield
With [bis(acetoxy)iodo]benzene; potassium acetate; palladium diacetate; N-acetylglycine In tert-butyl alcohol at 100℃; for 12h; Sealed tube;	63%
With isopropylmagnesium bromide; triphenylphosphine; cobalt(II) chloride In tetrahydrofuran at 20℃; for 18h; Green chemistry;	41%
With [bis(acetoxy)iodo]benzene; palladium diacetate; potassium carbonate; N-acetylglycine In tert-butyl alcohol at 100℃; for 20h; Inert atmosphere;	26%

2-(4-bromophenyl)-2-methylpropionic acid (32454-35-6) + 4-[4-(hydroxydiphenylmethyl)piperidin-1-yl]butyraldehyde (105955-84-8) → fexofenadine (83799-24-0)

Conditions	Yield
Stage #1: 2-(4-bromophenyl)-2-methylpropionic acid With sodium hydride In tetrahydrofuran at 25℃; for 0.5h; deprotonation; Stage #2: With tert.-butyl lithium In tetrahydrofuran at -72℃; for 0.916667h; Metallation; Stage #3: 4-[4-(hydroxydiphenylmethyl)piperidin-1-yl]butyraldehyde In tetrahydrofuran at -72℃; for 2.5h; Condensation;	60%

1,2,3-triazole (288-36-8) + 2-(4-bromophenyl)-2-methylpropionic acid (32454-35-6) → 2-(2-(4-bromophenyl)propan-2-yl)oxazole (1236409-17-8)

Conditions	Yield
Stage #1: 2-(4-bromophenyl)-2-methylpropionic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 2h; Stage #2: 1,2,3-triazole With potassium carbonate In sulfolane at 120℃; for 1h;	43%

2-(4-bromophenyl)-2-methylpropionic acid (32454-35-6) + trans-β-chloroacrylonitrile (871-29-4, 3721-37-7, 3721-38-8) → 2-[4-((E)-2-cyano-ethenesulfonyl)phenyl]-2-methylpropionic acid (1356089-38-7)

Conditions	Yield
Stage #1: 2-(4-bromophenyl)-2-methylpropionic acid With phenyllithium In tetrahydrofuran; toluene at -80℃; for 0.0833333h; Inert atmosphere; Stage #2: With n-butyllithium In tetrahydrofuran; hexane; toluene for 0.333333h; Inert atmosphere; Stage #3: trans-β-chloroacrylonitrile Further stages;	43%

2-(4-bromophenyl)-2-methylpropionic acid (32454-35-6) → 4-(1-hydroxy-2-methylpropan-2-yl)benzoic acid (75492-21-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: LiAlH4; diethyl ether 2: butyl lithium; diethyl ether / anschliessend Behandeln mit CO2 View Scheme

(S)-N-(1-cyanocyclopropyl)-4-fluoro-4-methyl-2-(((S)-2,2,2-trifluoro-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)amino)pentanamide (847358-99-0) + 2-(4-bromophenyl)-2-methylpropionic acid (32454-35-6) → 4'-[(1S)-1-[[(1S)-1-[[(1-cyanocyclopropyl)amino]carbonyl]-3-fluoro-3-methylbutyl]amino]-2,2,2-trifluoroethyl]-α,α-dimethyl-[1,1'-biphenyl]-4-acetic acid

Conditions	Yield
With sodium carbonate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride In DMF (N,N-dimethyl-formamide); water at 80℃; for 3h;

trans-4-aminoadamantan-1-carboxylic acid methyl ester hydrochloride + 2-(4-bromophenyl)-2-methylpropionic acid (32454-35-6) → E-4-[2-(4-bromo-phenyl)-2-methyl-propionylamino]-adamantane-1-carboxylic acid methyl ester

Conditions	Yield
With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 16h;

2-(4-bromophenyl)-2-methylpropionic acid (32454-35-6) → 2-(4-bromophenyl)-2-methylpropanoic acid chloride (1040860-77-2)

Conditions	Yield
With thionyl chloride for 2h; Heating / reflux;

2-(4-bromophenyl)-2-methylpropionic acid (32454-35-6) → C24H34O3Si

Conditions	Yield
Multi-step reaction with 4 steps 1.1: lithium aluminium tetrahydride / diethyl ether / -78 - 23 °C 2.1: 1H-imidazole / dichloromethane / 23 °C 3.1: n-butyllithium / tetrahydrofuran / -78 °C 3.2: 23 °C 4.1: tetrakis(triphenylphosphine) palladium(0); caesium carbonate / 1,2-dimethoxyethane / 100 °C View Scheme

2-(4-bromophenyl)-2-methylpropionic acid (32454-35-6) → C22H39BO3Si (1322094-75-6)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: lithium aluminium tetrahydride / diethyl ether / -78 - 23 °C 2.1: 1H-imidazole / dichloromethane / 23 °C 3.1: n-butyllithium / tetrahydrofuran / -78 °C 3.2: 23 °C View Scheme

2-(4-bromophenyl)-2-methylpropionic acid (32454-35-6) → C23H32O3Si (1322094-76-7)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: lithium aluminium tetrahydride / diethyl ether / -78 - 23 °C 2.1: 1H-imidazole / dichloromethane / 23 °C 3.1: n-butyllithium / tetrahydrofuran / -78 °C 3.2: 23 °C 4.1: tetrakis(triphenylphosphine) palladium(0); caesium carbonate / 1,2-dimethoxyethane / 100 °C 5.1: lithium hydroxide monohydrate / tetrahydrofuran; methanol; water / 23 °C View Scheme

2-(4-bromophenyl)-2-methylpropionic acid (32454-35-6) → 2-[4-((E)-2-cyano-ethenesulfonyl)phenyl]-N-prop-2-ynylisobutyramide (1365091-34-4)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: phenyllithium / tetrahydrofuran; toluene / 0.08 h / -80 °C / Inert atmosphere 1.2: 0.33 h / Inert atmosphere 2.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: phenyllithium / toluene; tetrahydrofuran / 0.08 h / -80 °C / Inert atmosphere 1.2: 0.33 h 1.3: 0.25 h 2.1: acetic acid / water; methanol / 20 °C 2.2: 1 h 3.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / dichloromethane / 1 h View Scheme

2-(4-bromophenyl)-2-methylpropionic acid (32454-35-6) → (E)-3-{4-[1,1-dimethyl-2-(4-methyl-piperazin-1-yl)-2-oxo-ethyl]-benzenesulfonyl}acrylonitrile (1365091-28-6)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: phenyllithium / tetrahydrofuran; toluene / 0.08 h / -80 °C / Inert atmosphere 1.2: 0.33 h / Inert atmosphere 2.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / tetrahydrofuran / 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: phenyllithium / toluene; tetrahydrofuran / 0.08 h / -80 °C / Inert atmosphere 1.2: 0.33 h 1.3: 0.25 h 2.1: acetic acid / water; methanol / 20 °C 2.2: 1 h 3.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / tetrahydrofuran / 20 °C View Scheme

2-(4-bromophenyl)-2-methylpropionic acid (32454-35-6) → 2-[4-((E)-2-cyano-ethenesulfonyl)phenyl]-N-pyridin-2-ylmethylisobutyramide (1365091-35-5)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: phenyllithium / tetrahydrofuran; toluene / 0.08 h / -80 °C / Inert atmosphere 1.2: 0.33 h / Inert atmosphere 2.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / tetrahydrofuran / 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: phenyllithium / toluene; tetrahydrofuran / 0.08 h / -80 °C / Inert atmosphere 1.2: 0.33 h 1.3: 0.25 h 2.1: acetic acid / water; methanol / 20 °C 2.2: 1 h 3.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / tetrahydrofuran / 20 °C View Scheme

Upstream product

• 826-55-1 2-methyl-2-phenylpropionic acid 
• 14062-25-0 Ethyl 4-bromophenylacetate 
• 74-88-4 methyl iodide 
• 101184-73-0 2-(4-bromophenyl)-2-methylpropanenitrile 
• 154825-97-5 methyl 2-(4-bromophenyl)-2,2-dimethylacetate 
• 32454-36-7 2-(4-bromophenyl)-2-methyl-propionic acid ethyl ester 
• 10519-96-7 potassium trimethylsilonate 
• 71-43-2 benzene 
• 53086-53-6 2-(4-bromophenyl)propionic acid 
• 41841-16-1 (4-bromo-phenyl)-acetic acid methyl ester 

Downstream Products

• 32454-37-8 2,2-dimethyl-2-(4-bromophenyl)ethanol 
• 83799-24-0 fexofenadine 
• 909187-36-6 2-methyl-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propanoic acid 
• 1040860-77-2 2-(4-bromophenyl)-2-methylpropanoic acid chloride 
• 154825-96-4 fexofenadine methyl ester 
• 154825-97-5 methyl 2-(4-bromophenyl)-2,2-dimethylacetate 
• 1394819-40-9 (E)-3-{4-[1-(1H-benzimidazol-2-yl)-1-methylethyl]benzenesulfonyl}acrylonitrile trifluoroacetic acid salt 
• 138452-21-8 fexofenadine hydrochloride 
• 169280-32-4 2-(4-{1-hydroxy-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butyl}phenyl)-2-methyl-1-(pyrrolidin-1-yl)propan-1-one 
• 578729-08-5 benzyl N-[1-(4-bromophenyl)-1-methylethyl]carbamate 

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