112704-79-7

Basic information

• Product Name: 4-Bromo-2-fluorobenzoic acid
• Synonyms: 4-Bromo-2-fluorobenzoic;4-Bromo-2-fluorobenzoic acid 98%;4-Bromo-2-fluorobenzoicacid98%;4-Bromo-2-fluorobenzoic acid ,99%;4-BroMo-2-fluorobenzoic acid, 98% 1GR;4-BroMo-2-fluorobenzoic acid, 98% 5GR;4 - broMine - 2 - fluoro benzoic acid;2-FLUORO-4-BROMOBENZOIC ACID
• CAS NO: 112704-79-7
• Molecular Formula: C₇H₄BrFO₂
• Molecular Weight: 219.01
• EINECS: -0
• Product Categories: Fluorin-contained Benzoic acid series;blocks;Bromides;Carboxes;FluoroCompounds;Aromatic Carboxylic Acids, Amides, Anilides, Anhydrides & Salts;Benzoic acid;Fluorobenzene;Acids & Esters;Bromine Compounds;Fluorine Compounds;Benzoic Acids (Building Blocks for Liquid Crystals);Building Blocks for Liquid Crystals;Functional Materials;C7;Carbonyl Compounds;Carboxylic Acids;Benzoic acid series;Fluorine series
• Mol File: 112704-79-7.mol
• Article Data: 8

Chemical Properties

• Melting Point: 211-215 °C(lit.)
• Boiling Point: 289.4 °C at 760 mmHg
• Flash Point: 128.8 °C
• Appearance: white to light yellow crystal powder
• Density: 1.7218 (rough estimate)
• Vapor Pressure: 0.0302mmHg at 25°C
• Refractive Index: 1.4240 (estimate)
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: Solubility in methanol, very faint turbidity.
• PKA: 3.04±0.10(Predicted)
• BRN: 6323931
• CAS DataBase Reference: 4-Bromo-2-fluorobenzoic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Bromo-2-fluorobenzoic acid(112704-79-7)
• EPA Substance Registry System: 4-Bromo-2-fluorobenzoic acid(112704-79-7)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 37/39-26
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 112704-79-7(Hazardous Substances Data)

Usage

Chemical Properties

white to light yellow crystal powder

Uses

Different sources of media describe the Uses of 112704-79-7 differently. You can refer to the following data:
1. 4-Bromo-2-fluorobenzoic Acid is a halogenated derivative of benzoic acid. 4-Bromo-2-fluorobenzoic Acid is used in the synthesis of pharmaceutically significant products such as d-Amino acid oxidase in hibitors.
2. 4-Bromo-2-fluorobenzoic acid may be used in the synthesis of biaryl intermediates by palladium-mediated coupling with various aryl boronic acids

General Description

4-Bromo-2-fluorobenzoic acid is a halogen substituted benzoic acid.

Synthetic route

sodium chlorite (7758-19-2) + Na2HPO4.12H2O + 4-bromo-2-fluorobenzaldehyde (57848-46-1) → 2-fluoro-4-bromobenzoic acid (112704-79-7)

Conditions	Yield
With dihydrogen peroxide In water; acetonitrile	96%

2-fluoro-4-bromotoluene (51436-99-8) → 2-fluoro-4-bromobenzoic acid (112704-79-7)

Conditions	Yield
With 2,2'-azobis(isobutyronitrile); oxygen; sodium bromide; cobalt(II) acetate; acetic acid In various solvent(s) at 110℃; under 760.051 Torr; for 4.5h;	91%
With 2,2'-azobis(isobutyronitrile); oxygen; cobalt(II) diacetate tetrahydrate; acetic acid; sodium bromide at 130℃; under 9000.9 Torr; for 1.5h; Green chemistry;	88%

carbon dioxide (124-38-9) + 2,5-dibromofluorobenzene (1435-52-5) → 2-fluoro-4-bromobenzoic acid (112704-79-7)

Conditions	Yield
With n-butyllithium; butyl magnesium bromide In tetrahydrofuran; hexane at 0℃;	90%

4-bromo-2-fluoroacetophenone (625446-22-2) → 2-fluoro-4-bromobenzoic acid (112704-79-7)

Conditions	Yield
With copper (II) nitrate tetrahydrate; oxygen In acetonitrile at 180℃; under 18751.9 Torr; for 1.5h; Green chemistry;	79%

4-bromo-2-fluoro-3-triethylsilanyl-benzoic acid → 2-fluoro-4-bromobenzoic acid (112704-79-7)

Conditions	Yield
With tetrabutyl ammonium fluoride In N,N-dimethyl-formamide at 155℃;

4-bromo-2-fluorobenzaldehyde (57848-46-1) → 2-fluoro-4-bromobenzoic acid (112704-79-7)

Conditions	Yield
With sodium chlorite; sodium dihydrogenphosphate; dihydrogen peroxide In water; acetonitrile at 20℃;

(2-bromo-6-fluorophenyl)triethylsilane (872545-52-3) → 2-fluoro-4-bromobenzoic acid (112704-79-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: BuLi / hexane; tetrahydrofuran / -75 °C 2: tetrabutylammonium fluoride trihydrate / dimethylformamide / 155 °C View Scheme

3-fluorobromobenzene (1073-06-9) → 2-fluoro-4-bromobenzoic acid (112704-79-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: 90 percent / BuLi / hexane; tetrahydrofuran / 2.75 h / -75 °C 2: BuLi / hexane; tetrahydrofuran / -75 °C 3: tetrabutylammonium fluoride trihydrate / dimethylformamide / 155 °C View Scheme

C10H12BrFO2Si → 2-fluoro-4-bromobenzoic acid (112704-79-7)

Conditions	Yield
With methanol; sodium hydroxide In water at 20 - 50℃; for 6h; Inert atmosphere;	5.6 g

2-fluoro-4-bromobenzoic acid (112704-79-7) → 4-bromo-2-fluorobenzoyl chloride (151982-51-3)

Conditions	Yield
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; for 3h; Inert atmosphere; Cooling with ice;	100%
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 1h;	100%
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; for 22h;	100%

N,O-dimethylhydroxylamine*hydrochloride (6638-79-5) + 2-fluoro-4-bromobenzoic acid (112704-79-7) → 2-fluoro-4-bromo-N-methoxy-N-methylbenzamide (801303-33-3)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20 - 40℃; for 47h;	100%
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In water at 0 - 5℃;	99%
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; Reagent/catalyst;	85%

methanol (67-56-1) + 2-fluoro-4-bromobenzoic acid (112704-79-7) → methyl 4-bromo-2-fluorobenzoate (179232-29-2)

Conditions	Yield
With sulfuric acid for 20h; Heating / reflux;	100%
Stage #1: 2-fluoro-4-bromobenzoic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane Stage #2: methanol In dichloromethane at 20℃; for 0.5h;	97%
With thionyl chloride at 0 - 20℃; for 12h;	96%

2,2'-dipyridyldisulphide (2127-03-9) + 2-fluoro-4-bromobenzoic acid (112704-79-7) → 4-Bromo-2-fluoro-thiobenzoic acid S-pyridin-2-yl ester (625446-21-1)

Conditions	Yield
With triphenylphosphine In dichloromethane at 0 - 20℃; for 4h;	100%

1-methyl-4-aminopiperidine (41838-46-4) + 2-fluoro-4-bromobenzoic acid (112704-79-7) → 4-bromo-2-fluoro-N-(1-methylpiperidin-4-yl)benzamide (893420-55-8)

Conditions	Yield
Stage #1: 4-Amino-1-methylpiperidine; 2-fluoro-4-bromobenzoic acid With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 1.5h; Stage #2: With sodium hydroxide In water at 20℃;	100%
With triethylamine; HATU In N,N-dimethyl-formamide

2-fluoro-4-bromobenzoic acid (112704-79-7) + diazomethyl-trimethyl-silane (18107-18-1) → methyl 4-bromo-2-fluorobenzoate (179232-29-2)

Conditions	Yield
In tetrahydrofuran; methanol; hexanes at 0 - 20℃; for 1h;	100%
In tetrahydrofuran; methanol at 0 - 20℃; for 1h;	88%
In methanol; diethyl ether; ethyl acetate at 20℃;

2,4-dimethyl-3-pentanol (600-36-2) + 2-fluoro-4-bromobenzoic acid (112704-79-7) → 2,4-dimethylpentan-3-yl 4-bromo-2-fluorobenzoate

Conditions	Yield
With dmap; camphor-10-sulfonic acid; dicyclohexyl-carbodiimide In dichloromethane at 20℃;	97%

2-fluoro-4-bromobenzoic acid (112704-79-7) → 4-bromo-N-tert-butyl-2-fluorobenzamide

Conditions	Yield
	96%

(S)-6,6'-bis[4-(trans-4-n-propylcyclohexyl)phenyl]-1,1'-bi-2-naphthol + 2-fluoro-4-bromobenzoic acid (112704-79-7) → (S)-6,6'-bis[4-(trans-4-n-propylcyclohexyl)phenyl]-1,1'-binaphthyl-2,2'-diyl bis(4-bromo-2-fluoro)benzoate

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 17h;	96%

2-fluoro-4-bromobenzoic acid (112704-79-7) + tert-butyl alcohol (75-65-0) → 4-bromo-2-fluoro-benzoic acid tert-butyl ester (889858-12-2)

Conditions	Yield
With dmap; di-tert-butyl dicarbonate In tetrahydrofuran at 80℃; for 13h;	95.5%
Stage #1: 2-fluoro-4-bromobenzoic acid With oxalyl dichloride; N,N-dimethyl-formamide In tetrahydrofuran at 0 - 20℃; for 1.5h; Stage #2: tert-butyl alcohol With pyridine In dichloromethane at 20℃; for 64h;	80%
Stage #1: 2-fluoro-4-bromobenzoic acid With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 20℃; for 5h; Stage #2: tert-butyl alcohol With pyridine In tetrahydrofuran at 0 - 50℃; for 23h;	74%

ethylamine (75-04-7) + 2-fluoro-4-bromobenzoic acid (112704-79-7) → 4-bromo-2-fluoro-N-ethylbenzamide

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; for 2h;	95%
Stage #1: 2-fluoro-4-bromobenzoic acid With thionyl chloride at 80℃; for 1.33333h; Stage #2: ethylamine In tetrahydrofuran; dichloromethane at 20℃; for 2h;	90%
Stage #1: 2-fluoro-4-bromobenzoic acid With thionyl chloride at 80℃; for 1.33333h; Stage #2: ethylamine In dichloromethane	849 mg

2-fluoro-4-bromobenzoic acid (112704-79-7) + methylamine (74-89-5) → 4-bromo-2-fluoro-N-methylbenzanamide (749927-69-3)

Conditions	Yield
Stage #1: 2-fluoro-4-bromobenzoic acid With thionyl chloride; N,N-dimethyl-formamide In Isopropyl acetate at 55℃; for 3h; Stage #2: methylamine With water In Isopropyl acetate at 0 - 35℃; for 12h;	94.4%
Stage #1: 2-fluoro-4-bromobenzoic acid With thionyl chloride In 1,2-dimethoxyethane at 0 - 50℃; Stage #2: methylamine In 1,2-dimethoxyethane at 35℃; for 0.5h; Solvent; Reagent/catalyst; Temperature;	93%
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 16h;	74%

(S)-dibenzyl 2-aminosuccinate 4-methylbenzenesulphonic acid salt + 2-fluoro-4-bromobenzoic acid (112704-79-7) → (S)-dibenzyl 2-(4-bromo-2-fluorobenzamido)succinate

Conditions	Yield
Stage #1: 2-fluoro-4-bromobenzoic acid With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane for 0.0833333h; Stage #2: (S)-dibenzyl 2-aminosuccinate 4-methylbenzenesulphonic acid salt In dichloromethane at 20℃; for 24h;	94%

2-(2-Hydroxyethyl)pyridine (103-74-2) + 2-fluoro-4-bromobenzoic acid (112704-79-7) → 2-(2-pyridyl)ethyl 4-bromo-2-fluorobenzoate (920270-28-6)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; Product distribution / selectivity;	93%
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 16h; Inert atmosphere;	93%
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 0 - 20℃; Product distribution / selectivity;	80%

2-fluoro-5-(trifluoromethyl)phenylboronic acid (352535-96-7) + 2-fluoro-4-bromobenzoic acid (112704-79-7) → 2',3-difluoro-5'-(trifluoromethyl)-[1,1'-biphenyl]-4-carboxylic acid

Conditions	Yield
With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); tricyclohexylphosphine In 1,4-dioxane at 100℃; for 1h; Microwave irradiation;	93%
With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); tricyclohexylphosphine In 1,4-dioxane at 120℃; for 1h; Microwave irradiation;	93%

phenylmethanethiol (100-53-8) + 2-fluoro-4-bromobenzoic acid (112704-79-7) → 2-(benzylthio)-4-bromobenzoic acid

Conditions	Yield
Stage #1: 2-fluoro-4-bromobenzoic acid With caesium carbonate In 1-methyl-pyrrolidin-2-one at 120℃; for 0.05h; Stage #2: phenylmethanethiol In 1-methyl-pyrrolidin-2-one at 20 - 120℃; for 3h;	93%

benzyl bromide (100-39-0) + 2-fluoro-4-bromobenzoic acid (112704-79-7) → benzyl 4-bromo-2-fluorobenzoate (437764-46-0)

Conditions	Yield
With sodium carbonate In N,N-dimethyl-formamide at 0 - 20℃; for 24h;	92%
With sodium carbonate In N,N-dimethyl-formamide at 0 - 20℃; for 16h;	89%
With potassium carbonate In N,N-dimethyl-formamide at 60℃; for 3h;

ethanol (64-17-5) + 2-fluoro-4-bromobenzoic acid (112704-79-7) → 4-bromo-2-fluorobenzoic acid ethyl ester (474709-71-2)

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 20h;	90%
With dmap; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide at 40 - 45℃; for 24h; Inert atmosphere;	90%
With sulfuric acid for 16h; Heating / reflux;

Upstream product

• 51436-99-8 2-fluoro-4-bromotoluene 
• 7758-19-2 sodium chlorite 
• 57848-46-1 4-bromo-2-fluorobenzaldehyde 
• 124-38-9 carbon dioxide 
• 1435-52-5 2,5-dibromofluorobenzene 
• 625446-22-2 4-bromo-2-fluoroacetophenone 
• 1073-06-9 3-fluorobromobenzene 
• 872545-52-3 (2-bromo-6-fluorophenyl)triethylsilane 

Downstream Products

• 151982-51-3 4-bromo-2-fluorobenzoyl chloride 
• 749927-69-3 4-bromo-2-fluoro-N-methylbenzanamide 
• 625446-21-1 4-Bromo-2-fluoro-thiobenzoic acid S-pyridin-2-yl ester 
• 749928-52-7 2-(4-bromo-2-fluorophenyl)propan-2-ol 
• 855482-51-8 4-bromo-2-cyclohexylaminobenzoic acid 
• 855481-84-4 4-bromo-2-(propan-2-ylamino)benzoic acid 
• 893420-55-8 4-bromo-2-fluoro-N-(1-methylpiperidin-4-yl)benzamide 
• 644984-78-1 4-bromo-2-ethylbenzoic acid 
• 192443-10-0 (4-bromo-2-fluorophenyl)(4-methoxyphenyl)methanone 
• 877383-80-7 3,5'-difluoro-2'-methoxy-[1,1'-biphenyl]-4-carboxylic acid 
• 913570-29-3 4-ethenyl-2-fluorobenzoic acid 
• 188582-62-9 4-bromo-2-fluorobenzyl alcohol 
• 72135-36-5 4-bromo-2-methoxybenzoic acid 
• 1099687-44-1 C₁₁H₁₃BrO₄ 

Relevant articles and documents

Synthesis method of 2-fluoro-4-halogen benzoic acid

The invention provides a synthesis method of 2-fluoro-4-halogen benzoic acid. The synthesis method comprises the following steps: (a) removing hydrogen from a substance shown in a formula (I) by using a lithium amide reagent or an alkyl lithium reagent (LDA, TMPLi, n-butyl lithium and the like), and reacting with trialkyl halosilane (TMSCl, TESCl, TBSCl and the like) to obtain a compound shown in a formula (II); (b) removing hydrogen from the compound represented by the formula (II) obtained in the step (a) by using a lithium amide reagent or an alkyl lithium reagent (LDA, TMPLi, n-butyl lithium and the like), and adding into dry ice/THF to react to obtain a compound represented by a formula (III); and (c) removing a trialkyl silane protecting group from the compound shown in the formula (III) obtained in the step (b) to obtain a compound shown in a formula (IV). According to the preparation method, starting raw materials, process routes and post-treatment processes are different, the raw materials are simple and easy to obtain, the cost is low, and the preparation method is suitable for laboratory small-scale preparation and industrial production.

INHIBITORS OF STEAROYL-COA DESATURASE

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Fluorine-flanked congested sites: Minimal, though perceptible buttressing effects on the proton mobility of arenes

(2,6-Difluorophenyl)trimethylsilane, -triethylsilane and -triisopropylsilane undergo sec-butyllithium-mediated metalation at the 3- and 4-position (ortho and meta relative to the halogen) in ratios of 99.6:0.4, 98:2 and 95:5, respectively. The steric pressure transmitted by the fluorine atoms can be increased if the trialkylsilyl group is locked up on the other side by a relatively voluminous substituent. Whereas (2,6-difluorophenyl)triethylsilane is attacked by lithium 2,2,6,6-tetramethylpiperidide under deprotonation of the 4- and 5-position in a ratio of 99.4:0.6, the proportion of "ortho"/ "meta" metalation changes to 84:16 when (2-bromo-6-fluorophenyl) triethylsilane acts as the substrate. Wiley-VCH Verlag GmbH & Co. KGaA, 2005.