261904-39-6

Basic information

• Product Name: (2R)-3-Bromo-2-hydroxy-2-methylpropanoic acid
• Synonyms: (R)-3-bromo-2-hydroxy-2-methylpropanoic acid;(2R)-3-Bromo-2-hydroxy-2-methylpropanoic acid;(2R)-3-Bromo-2-hydroxy-2-methylpropionic acid;(R)-3-Bromo-2-hydroxy-2-methylpropionic Acid;(R)-3-Bromo-2-hydroxy-2-methylpropionic Acid
• CAS NO: 261904-39-6
• Molecular Formula: C₄H₇BrO₃
• Molecular Weight: 183
• Mol File: 261904-39-6.mol
• Article Data: 37

Chemical Properties

• Melting Point: 113.0 to 117.0 °C
• Boiling Point: 294.474 °C at 760 mmHg
• Flash Point: 131.893 °C
• Appearance: /
• Density: 1.831 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.541
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: Chloroform, Methanol
• PKA: 3.39±0.16(Predicted)
• CAS DataBase Reference: (2R)-3-Bromo-2-hydroxy-2-methylpropanoic acid(CAS DataBase Reference)
• NIST Chemistry Reference: (2R)-3-Bromo-2-hydroxy-2-methylpropanoic acid(261904-39-6)
• EPA Substance Registry System: (2R)-3-Bromo-2-hydroxy-2-methylpropanoic acid(261904-39-6)

Safety Data

• Hazard Codes: Xi
• Statements: 36/38
• Safety Statements: 26
• RIDADR: UN 3261 8/PG III
• HazardClass: 8
• PackingGroup: III
• Hazardous Substances Data: 261904-39-6(Hazardous Substances Data)

Usage

Uses

(2R)-3-Bromo-2-hydroxy-2-methylpropionic Acid is used as a reagent in the synthesis of [18F]-radiolabeled hydroxyflutamide derivatives as prostate cancer PET imaging agents.

InChI:InChI=1/C4H7BrO3/c1-4(8,2-5)3(6)7/h8H,2H2,1H3,(H,6,7)/t4-/m0/s1

Synthetic route

(3R,8AR)-3-Bromomethyl-3-methyl-tetrahydro-pyrrolo[2,1-c][1,4]oxazine-1,4-dione (106138-80-1) → (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid (261904-39-6)

Conditions	Yield
With hydrogen bromide for 5h; Reflux;	91.3%
With hydrogen bromide In water for 1h; Heating / reflux;	86%
With water; hydrogen bromide for 1h; Heating / reflux;	86%

(3R,8αR)-3-(bromomethyl)-3-methyl-tetrahydro-3H-pyrrolo[2,1-c][1,4]oxazine-1,4-dione → (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid (261904-39-6)

Conditions	Yield
With water; hydrogen bromide for 1h; Heating / reflux;	85%
With hydrogen bromide at 105℃; for 1.5h;	84%
With hydrogen bromide In water at 105℃; Temperature; Large scale;

3-bromomethyl-3-methyl-tetrahydro-pyrrolo[2,1-c][1,4]oxazine-1,4-dione → (2R)-3-chloro-2-hydroxy-2-methylpropanoic acid + (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid (261904-39-6)

Conditions	Yield
With hydrogenchloride Hydrolysis; Heating; Title compound not separated from byproducts.;

C9H15BrO3 (1250440-74-4) → (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid (261904-39-6)

Conditions	Yield
With hydrogenchloride In water for 4h; Reflux; Inert atmosphere;
With hydrogenchloride; water for 4h; Reflux;

(2R)-1-methacryloylpyrrolidin-2-carboxylic acid (106089-24-1) → (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid (261904-39-6)

Conditions	Yield
Stage #1: (2R)-1-methacryloylpyrrolidin-2-carboxylic acid With N-Bromosuccinimide In N,N-dimethyl-formamide Stage #2: With hydrogenchloride In water at 100℃;

3-pentafluorosulfuraniline (2993-22-8) + (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid (261904-39-6) → (R)-3-bromo-2-hydroxy-2-methyl-N-(3-(pentafluorosulfanyl)phenyl)propanamide

Conditions	Yield
Stage #1: (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid With thionyl chloride In N,N-dimethyl acetamide at -10 - -5℃; for 3h; Inert atmosphere; Stage #2: 3-pentafluorosulfuraniline In N,N-dimethyl acetamide at 20℃; for 16h; Inert atmosphere;	96%

5-amino-2-cyanopyridine (55338-73-3) + (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid (261904-39-6) → (2R)-3-bromo-N-(6-cyanopyridin-3-yl)-2-hydroxy-2-methylpropanamide

Conditions	Yield
With thionyl chloride; trimethylamine	92%
Stage #1: (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid With thionyl chloride In tetrahydrofuran at 0 - 12℃; for 2.166h; Stage #2: With triethylamine In tetrahydrofuran at -5 - 12℃; for 0.333333h; Stage #3: 5-amino-2-cyanopyridine In tetrahydrofuran at 50℃; for 2h;	85%

5-amino-3-(trifluoromethyl)-2-pyridinecarbonitrile (573762-62-6) + (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid (261904-39-6) → (R)-3-bromo-N-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-2-hydroxy-2-methylpropanamide

Conditions	Yield
With thionyl chloride; trimethylamine	90%
Stage #1: (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid With thionyl chloride In tetrahydrofuran at 0 - 12℃; for 2.166h; Stage #2: With triethylamine In tetrahydrofuran at -5 - 12℃; for 0.333333h; Stage #3: 5-amino-3-(trifluoromethyl)pyridine-2-carbonitrile In tetrahydrofuran at 50℃; for 2h;	85%
Stage #1: (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid With thionyl chloride In tetrahydrofuran at 4℃; for 3h; Inert atmosphere; Stage #2: With triethylamine In tetrahydrofuran at 4℃; for 0.333333h; Inert atmosphere; Stage #3: 5-amino-3-(trifluoromethyl)pyridine-2-carbonitrile In tetrahydrofuran at 20℃;	70.2%

bromal (115-17-3) + (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid (261904-39-6) → C7H8Br4O3 (1003838-02-5)

Conditions	Yield
With sulfuric acid at 0 - 20℃;	89%

4-amino-2-chlorobenzonitrile (20925-27-3) + (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid (261904-39-6) → (2R)-3-bromo-N-(3-chloro-4-cyanophenyl)-2-hydroxy-2-methylpropanamide (1002330-78-0)

Conditions	Yield
Stage #1: (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid With thionyl chloride In tetrahydrofuran at 0 - 12℃; for 2.166h; Stage #2: With triethylamine In tetrahydrofuran at -5 - 12℃; for 0.333333h; Stage #3: 4-amino-2-chlorobenzonitrile In tetrahydrofuran at 50℃; for 2h;	88.6%
Stage #1: (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid With thionyl chloride In tetrahydrofuran at 4℃; for 3h; Inert atmosphere; Stage #2: 4-amino-2-chlorobenzonitrile With triethylamine In tetrahydrofuran at 20℃;	73%
Stage #1: (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid With thionyl chloride In tetrahydrofuran at 4℃; for 3h; Inert atmosphere; Stage #2: In tetrahydrofuran for 0.333333h; Inert atmosphere; Stage #3: 4-amino-2-chlorobenzonitrile In tetrahydrofuran at 20℃; Inert atmosphere;	73%
Stage #1: (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid With thionyl chloride In tetrahydrofuran at 4℃; for 3h; Inert atmosphere; Stage #2: 4-amino-2-chlorobenzonitrile With triethylamine In tetrahydrofuran at 20℃;	49.4%
With thionyl chloride In tetrahydrofuran at 0℃;

4-(pentafluorosulfanyl)aniline (2993-24-0) + (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid (261904-39-6) → (R)-3-bromo-2-hydroxy-2-methyl-N-(4-(pentafluorosulfanyl)phenyl)propanamide

Conditions	Yield
Stage #1: (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid With thionyl chloride In N,N-dimethyl acetamide at -10 - -5℃; for 3h; Inert atmosphere; Stage #2: 4-(pentafluorosulfanyl)aniline In N,N-dimethyl acetamide at 20℃; for 16h; Inert atmosphere;	88%

4-amino-2-trifluoromethylbenzonitrile (654-70-6) + (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid (261904-39-6) → (2R)-3-bromo-N-[4-cyano-3-(trifluoromethyl)phenyl]-2-hydroxy-2-methylpropanamide (206193-17-1)

Conditions	Yield
Stage #1: (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid With thionyl chloride In N,N-dimethyl acetamide at -10℃; for 3h; Inert atmosphere; Stage #2: 4-amino-2-trifluoromethylbenzonitrile In N,N-dimethyl acetamide at -10 - 20℃; for 16h; Inert atmosphere;	84%
Stage #1: (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid With thionyl chloride In ISOPROPYLAMIDE at -10℃; Inert atmosphere; Stage #2: 4-amino-2-trifluoromethylbenzonitrile In ISOPROPYLAMIDE at 20℃;	84%
With thionyl chloride In N,N-dimethyl acetamide at -15 - 40℃; for 3.5h;	80.4%

ethanol (64-17-5) + (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid (261904-39-6) → (R)-3-bromo-2-hydroxy-2-methyl-propionic acid ethyl ester

Conditions	Yield
With toluene-4-sulfonic acid for 7h; Reflux;	83%

4-nitro-3-(trifluoromethyl)benzeneamine (393-11-3) + (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid (261904-39-6) → N-[4-nitro-3-(trifluoromethyl)phenyl]-(2R)-3-bromo-2-hydroxy-2-methylpropanamide (206193-18-2)

Conditions	Yield
With thionyl chloride In N,N-dimethyl acetamide at 20℃;	80%
Stage #1: (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid With thionyl chloride In dimethyl amine at -10 - -5℃; for 2h; Stage #2: 4-nitro-3-(trifluoromethyl)benzeneamine In dimethyl amine at 20℃;	80%
Stage #1: (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid With thionyl chloride In 2,4-dichlorophenoxyacetic acid dimethylamine at -10℃; for 2h; Stage #2: 4-nitro-3-(trifluoromethyl)benzeneamine In 2,4-dichlorophenoxyacetic acid dimethylamine at 20℃;	80%
Stage #1: (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid With thionyl chloride In tetrahydrofuran at 10℃; for 2.83333h; Inert atmosphere; Large scale; Stage #2: 4-nitro-3-(trifluoromethyl)benzeneamine With triethylamine In tetrahydrofuran at 10 - 50℃; for 18.75h; Large scale;	70.3%
With thionyl chloride In N,N-dimethyl acetamide at -15 - 40℃; for 8.5h;	57.2%

4-amino-5-iodo-2-(trifluoromethyl)benzonitrile (852569-35-8) + (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid (261904-39-6) → (R)-3-bromo-N-(4-cyano-2-iodo-5-(trifluoromethyl)phenyl)-2-hydroxy-2-methylpropanamide

Conditions	Yield
With thionyl chloride; triethylamine	64.6%

4-amino-2-(pentafluorosulfanyl)benzonitrile (852469-69-3) + (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid (261904-39-6) → (R)-3-bromo-N-(4-cyano-3-(pentafluorosulfanyl)phenyl)-2-hydroxy-2-methylpropanamide

Conditions	Yield
Stage #1: (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid With thionyl chloride In N,N-dimethyl acetamide at -10 - -5℃; for 3h; Inert atmosphere; Stage #2: 4-amino-2-(pentafluorosulfanyl)benzonitrile In N,N-dimethyl acetamide at 20℃; for 16h; Inert atmosphere;	49%

4-Amino-2-chloropyridine (14432-12-3) + (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid (261904-39-6) → (R)-3-bromo-N-(2-chloropyridin-4-yl)-2-hydroxy-2-methylpropanamide

Conditions	Yield
Stage #1: (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid With thionyl chloride In tetrahydrofuran at 4℃; for 3h; Inert atmosphere; Stage #2: With triethylamine In tetrahydrofuran at 4℃; for 0.333333h; Stage #3: 4-Amino-2-chloropyridine In tetrahydrofuran at 4 - 20℃;	43%

2-fluorophenol (367-12-4) + (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid (261904-39-6) → C10H11FO4 (1578263-99-6)

Conditions	Yield
With potassium carbonate In butanone for 16h; Reflux;	15%

(2R)-3-bromo-2-hydroxy-2-methylpropanoic acid (261904-39-6) → (R)-3-bromo-2-hydroxy-2-methylpropanoyl chloride (1010396-30-1)

Conditions	Yield
With thionyl chloride In tetrahydrofuran at 0℃;
With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at -10 - -5℃; for 3h;
With thionyl chloride In tetrahydrofuran at 0℃;

bromoacid + 4-nitro-3-(trifluoromethyl)benzeneamine (393-11-3) + (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid (261904-39-6) → N-[4-nitro-3-(trifluoromethyl)phenyl]-(2R)-3-bromo-2-hydroxy-2-methylpropanamide (206193-18-2)

Conditions	Yield
With thionyl chloride In 2,4-dichlorophenoxyacetic acid dimethylamine	18.0 g (80%)
With thionyl chloride In 2,4-dichlorophenoxyacetic acid dimethylamine	18.0 g (80%)
With thionyl chloride In 2,4-dichlorophenoxyacetic acid dimethylamine	18.0 g (80%)

dimethyl amine (124-40-3) + (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid (261904-39-6) → C6H13NO3 (936910-33-7)

Conditions	Yield
In tetrahydrofuran at 0℃; for 2h;

4-nitro-3-methylaniline (611-05-2) + (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid (261904-39-6) → (2R)-3-bromo-2-hydroxy-2-methyl-N-(3-methyl-4-nitrophenyl)propionamide (821764-69-6)

Conditions	Yield
Stage #1: (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid With thionyl chloride In ISOPROPYLAMIDE at -10 - -5℃; for 2h; Heating / reflux; Stage #2: 4-nitro-3-methylaniline In ISOPROPYLAMIDE at 20℃; for 3h;

CH2Cl2/EtOAc + 4-amino-2-trifluoromethylbenzonitrile (654-70-6) + (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid (261904-39-6) → (2R)-3-bromo-N-[4-cyano-3-(trifluoromethyl)phenyl]-2-hydroxy-2-methylpropanamide (206193-17-1) + (3R,8AR)-3-Bromomethyl-3-methyl-tetrahydro-pyrrolo[2,1-c][1,4]oxazine-1,4-dione (106138-80-1)

Conditions	Yield
With thionyl chloride; triethylamine In tetrahydrofuran; water	A n/a B 55.8 g (73.9%)

CH2Cl2/EtOAc + 4-amino-2-trifluoromethylbenzonitrile (654-70-6) + (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid (261904-39-6) → (2R)-3-bromo-N-[4-cyano-3-(trifluoromethyl)phenyl]-2-hydroxy-2-methylpropanamide (206193-17-1)

Conditions	Yield
With thionyl chloride; triethylamine In tetrahydrofuran; water	55.8 g (73.9%)

4-Fluorophenol (371-41-5) + (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid (261904-39-6) → C10H11FO4

Conditions	Yield
With potassium carbonate In butanone for 16h; Reflux;

4-Fluorothiophenol (371-42-6) + (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid (261904-39-6) → (R)-3-(4-fluorophenylmercapto)-2-hydroxy-2-methylpropionic acid (335595-52-3)

Conditions	Yield
With sodium hydroxide In isopropyl alcohol

6-amino-quinazoline (101421-72-1) + (2R)-3-bromo-2-hydroxy-2-methylpropanoic acid (261904-39-6) → (R)-3-bromo-2-hydroxy-2-methyl-N-(quinazolin-6-yl) propanamide

Conditions	Yield
With thionyl chloride; trimethylamine	0.71 g

Upstream product

• 106089-24-1 (2R)-1-methacryloylpyrrolidin-2-carboxylic acid 
• 1250440-74-4 C₉H₁₅BrO₃ 
• 927203-28-9 (3R,8αR)-3-(bromomethyl)-3-methyl-tetrahydro-3H-pyrrolo[2,1-c][1,4]oxazine-1,4-dione 
• 106138-80-1 (3R,8AR)-3-Bromomethyl-3-methyl-tetrahydro-pyrrolo[2,1-c][1,4]oxazine-1,4-dione 
• 927203-28-9 3-bromomethyl-3-methyl-tetrahydro-pyrrolo[2,1-c][1,4]oxazine-1,4-dione 

Downstream Products

• 821764-69-6 (2R)-3-bromo-2-hydroxy-2-methyl-N-(3-methyl-4-nitrophenyl)propionamide 
• 206193-17-1 (2R)-3-bromo-N-[4-cyano-3-(trifluoromethyl)phenyl]-2-hydroxy-2-methylpropanamide 
• 106138-80-1 (3R,8AR)-3-Bromomethyl-3-methyl-tetrahydro-pyrrolo[2,1-c][1,4]oxazine-1,4-dione 
• 335595-52-3 (R)-3-(4-fluorophenylmercapto)-2-hydroxy-2-methylpropionic acid 
• 1002330-78-0 (2R)-3-bromo-N-(3-chloro-4-cyanophenyl)-2-hydroxy-2-methylpropanamide 
• 1578263-99-6 C₁₀H₁₁FO₄ 
• 206193-18-2 N-[4-nitro-3-(trifluoromethyl)phenyl]-(2R)-3-bromo-2-hydroxy-2-methylpropanamide 

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