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

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

Used in Pharmaceutical Industry:
(2R)-3-Bromo-2-hydroxy-2-methylpropanoic acid is used as a key reagent for the synthesis of [18F]-radiolabeled hydroxyflutamide derivatives. These derivatives serve as valuable imaging agents in the field of medical diagnostics, specifically for Positron Emission Tomography (PET) imaging of prostate cancer. The compound's unique structure allows for the development of targeted radiotracers that can help in the early detection, staging, and monitoring of prostate cancer progression, ultimately aiding in the effective treatment of the disease.

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

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

Downstream Products

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

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