2106-04-9

Basic information

• Product Name: 3-Chloro-2-fluoroaniline
• Synonyms: 3-CHLORO-2-FLUOROANILINE;BUTTPARK 29\01-51;TIMTEC-BB SBB004108;3-Chloro-2-fluoroaniline 97%;3-Chloro-2-fluoroaniline97%;3-chloro-2-fluoro-benzenamin;3-Chloro-2-fluoroaniline,98%;3-Amino-2-fluorochlorobenzene
• CAS NO: 2106-04-9
• Molecular Formula: C₆H₅ClFN
• Molecular Weight: 145.56
• EINECS: 218-283-6
• Product Categories: Anilines, Aromatic Amines and Nitro Compounds;Aniline;Amines;C2 to C6;Nitrogen Compounds
• Mol File: 2106-04-9.mol

Chemical Properties

• Boiling Point: 214 °C(lit.)
• Flash Point: 230 °F
• Appearance: clear light beige liquid
• Density: 1.324 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.125mmHg at 25°C
• Refractive Index: n20/D 1.564(lit.)
• Storage Temp.: Keep in dark place,Inert atmosphere,Room temperature
• PKA: 2.15±0.10(Predicted)
• CAS DataBase Reference: 3-Chloro-2-fluoroaniline(CAS DataBase Reference)
• NIST Chemistry Reference: 3-Chloro-2-fluoroaniline(2106-04-9)
• EPA Substance Registry System: 3-Chloro-2-fluoroaniline(2106-04-9)

Safety Data

• Hazard Codes: Xi,T,Xn
• Statements: 36/37/38-20/21/22-41-37/38-22-23/24/25
• Safety Statements: 26-36-36/37/39-39-45
• WGK Germany: 3
• TSCA: Yes
• HazardClass: 6.1
• Hazardous Substances Data: 2106-04-9(Hazardous Substances Data)

Usage

Uses

Used in Chemical Synthesis:
3-Chloro-2-fluoroaniline is used as a key intermediate in the synthesis of various organic compounds. Its unique dihalo-substituted structure allows for the creation of a range of products with different functional groups and properties.
Used in Pharmaceutical Industry:
3-Chloro-2-fluoroaniline is used as a building block for the development of pharmaceutical compounds. It is specifically utilized in the preparation of 2-chloro-3-fluorobromobenzene and 4-((3-chloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl acetate, which are important intermediates in the synthesis of potential therapeutic agents.
These applications highlight the versatility of 3-Chloro-2-fluoroaniline in both the chemical and pharmaceutical industries, where its unique properties and reactivity contribute to the development of new and innovative products.

InChI:InChI=1/C6H5ClFN/c7-4-2-1-3-5(9)6(4)8/h1-3H,9H2

Synthetic route

1-chloro-2-fluoro-3-nitrobenzene (2106-49-2) → 3-chloro-2-fluoroaniline (2106-04-9)

Conditions	Yield
With iron

1,2-Dichloro-3-nitrobenzene (3209-22-1) → 3-chloro-2-fluoroaniline (2106-04-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: dimethylformamide; potassium fluoride / 150 °C 2: iron View Scheme

4-chloro-7-methoxy-6-{[(2S)-1-tert-butoxycarbonylpyrrolidin-2-yl]methoxy}quinazoline + 3-chloro-2-fluoroaniline (2106-04-9) → 4-(3-chloro-2-fluoroanilino)-7-methoxy-6-{[(2S)-pyrrolidin-2-yl]methoxy}quinazoline hydrochloride

Conditions	Yield
With hydrogenchloride In 1,4-dioxane for 1h; Heating / reflux;	100%

3-chloro-2-fluoroaniline (2106-04-9) + acetic anhydride (108-24-7) → N-(3-chloro-2-fluorophenyl)acetamide (395-36-8)

Conditions	Yield
for 2h; Reflux;	100%
With sodium hydroxide; acetic acid

3-chloro-2-fluoroaniline (2106-04-9) + 6-acetoxy-4-chloro-7-methoxyquinazoline (230955-75-6) → 4-((3-chloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl acetate (740081-22-5)

Conditions	Yield
In acetonitrile at 80℃;	99%
In isopropyl alcohol Heating;	98%
In isopropyl alcohol for 3h; Reflux;	93%

3-chloro-2-fluoroaniline (2106-04-9) + 4-chloro-6-nitro-7-methoxyquinazoline (55496-69-0) → 4-[(3-chloro-2-fluorophenyl)amino]-7-methoxy-6-nitroquinazoline

Conditions	Yield
In acetonitrile at 80℃; for 0.5h;	99%
With acetic acid; triethylamine for 48h;	94%

3-chloro-2-fluoroaniline (2106-04-9) + Ethyl oxalyl chloride (4755-77-5) → ethyl 2-((3-chloro-2-fluorophenyl)amino)-2-oxoacetate

Conditions	Yield
With triethylamine In tetrahydrofuran at 0 - 20℃; for 1h;	98%

4-chloro-7-fluoro-6-nitroquinazoline hydrochloride (1000397-30-7) + 3-chloro-2-fluoroaniline (2106-04-9) → N-(3-chloro-2-fluorophenyl)-7-fluoro-6-nitroquinazolin-4-amine hydrochloride (1000397-23-8)

Conditions	Yield
In isopropyl alcohol at 80℃; for 3h;	97%
In isopropyl alcohol Reflux;

3-chloro-2-fluoroaniline (2106-04-9) + orthoformic acid triethyl ester (122-51-0) → N,N'-bis(3-chloro-2-fluoro-phenyl)formamidine (1252041-51-2)

Conditions	Yield
With acetic acid In cyclohexane at 48℃; for 6h; Inert atmosphere; Industrial scale;	96.2%
With acetic acid In cyclohexane at 48℃; for 12h;	93%

3-chloro-2-fluoroaniline (2106-04-9) + 7-benzyloxy-4-chloro-6-methoxyquinazoline (162364-72-9) → 7-(benzyloxy)-N-(3-chloro-2-fluorophenyl)-6-methoxyquinazolin-4-amine hydrochloride (848415-65-6)

Conditions	Yield
With hydrogenchloride In 1,4-dioxane at 80℃;	96%

3-chloro-2-fluoroaniline (2106-04-9) + 6-bromo-4-chloro-7-fluoropyrido[3,2-d]pyrimidine → 6-bromo-N-(3-chloro-2-fluorophenyl)-7-fluoropyrido[3,2-d]pyrimidin-4-amine

Conditions	Yield
In acetonitrile at 25℃; for 1h;	96%

3-chloro-2-fluoroaniline (2106-04-9) + 6-acetoxy-4-chloro-7-methoxyquinazoline (230955-75-6) → 4-((3-chloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-ol (612501-52-7)

Conditions	Yield
With hydrogenchloride In acetonitrile for 1h; Product distribution / selectivity; Heating / reflux;	95%

4-chloro-6-iodoquinazoline (98556-31-1) + 3-chloro-2-fluoroaniline (2106-04-9) → N-(3-chloro-2-fluorophenyl)-6-iodoquinazolin-4-amine

Conditions	Yield
In isopropyl alcohol at 80℃; for 2h;	95%

3-chloro-2-fluoroaniline (2106-04-9) + N,N-dimethyl-formamide dimethyl acetal (4637-24-5) → N'-(3-chloro-2-fluoro-phenyl)-N,N-dimethyl-formamidine (1252041-52-3)

Conditions	Yield
With acetic acid In 2-methyltetrahydrofuran at 76℃; for 3h;	93%

3-chloro-2-fluoroaniline (2106-04-9) + 6-acetoxy-4-chloro-7-methoxyquinazoline (230955-75-6) → 4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl acetate monohydrochloride (612501-80-1)

Conditions	Yield
In isopropyl alcohol at 80℃; for 3h; Heating / reflux;	92%
In isopropyl alcohol at 80℃; for 3h;	92%
In isopropyl alcohol at 80℃; for 3h; Inert atmosphere;	92%

6-[1-(tert-butoxycarbonyl)piperidin-3-yloxy]-4-chloro-7-methoxyquinazoline (612501-69-6) + 3-chloro-2-fluoroaniline (2106-04-9) → 4-(3-chloro-2-fluoroanilino)-7-methoxy-6-(piperidin-3-yloxy)quinazoline dihydrochloride

Conditions	Yield
With hydrogenchloride In 1,4-dioxane; acetonitrile for 1h; Heating / reflux;	91%

ethyl 4-chloro-6,7-dimethoxycinnoline-3-carboxylatre (1041853-11-5) + 3-chloro-2-fluoroaniline (2106-04-9) → ethyl 4-[(3-chloro-2-fluorophenyl)amino]-6,7-dimethoxycinnoline-3-carboxylate (1041853-33-1)

Conditions	Yield
With acetic acid In ethanol at 75℃;	88%

3-chloro-2-fluoroaniline (2106-04-9) + benzoyl chloride (98-88-4) → N-(3-chloro-2-fluorophenyl)benzamide

Conditions	Yield
With sodium hydroxide In water; toluene at 60℃; for 2h; pH=8;	87%

3-chloro-2-fluoroaniline (2106-04-9) + potassium ethyl xanthogenate (140-89-6) → 2-mercapto-7-chlorobenzothiazole (1849-73-6)

Conditions	Yield
In N,N-dimethyl-formamide at 120 - 130℃; Inert atmosphere;	87%

3-chloro-2-fluoroaniline (2106-04-9) + ethyl 5-chloro-1-(3,5-difluorobenzyl)-4-(2-oxoethyl)-1H-pyrazole-3-carboxylate → ethyl 5-chloro-4-(2-((3-chloro-2-fluorophenyl)amino)ethyl)-1-(3,5-difluorobenzyl)-1H-pyrazole-3-carboxylate

Conditions	Yield
Stage #1: 3-chloro-2-fluoroaniline; ethyl 5-chloro-1-(3,5-difluorobenzyl)-4-(2-oxoethyl)-1H-pyrazole-3-carboxylate With acetic acid In 1,2-dichloro-ethane for 0.166667h; Stage #2: With sodium tris(acetoxy)borohydride In 1,2-dichloro-ethane at 30℃; for 3h;	86%

3-chloro-2-fluoroaniline (2106-04-9) + 4-chloro-7,8-dihydro[1,4]-dioxino[2,3-g]quinazoline (52791-05-6) → N-(3-chloro-2-fluorophenyl)-7,8-dihydro[1,4]dioxino[2,3-g]quinazolin-4-amine

Conditions	Yield
Stage #1: 3-chloro-2-fluoroaniline; 4-chloro-7,8-dihydro[1,4]-dioxino[2,3-g]quinazoline In isopropyl alcohol at 80℃; Microwave irradiation; Stage #2: With sodium hydrogencarbonate In water	85%
In N,N-dimethyl-formamide for 24h; Inert atmosphere; Heating;	82%
In N,N-dimethyl-formamide at 60℃; for 24h;	82%

3-chloro-2-fluoroaniline (2106-04-9) + (3S)-1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid (88495-54-9) → C12H14ClFN2O

Conditions	Yield
Stage #1: 3-chloro-2-fluoroaniline; (3S)-1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid With dmap; dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃; for 13h; Inert atmosphere; Stage #2: With trifluoroacetic acid In dichloromethane at 0 - 20℃; for 22h; Inert atmosphere;	85%

3-chloro-2-fluoroaniline (2106-04-9) + (1-adamantyl)methyl isocyanate (69887-12-3) → 1-(adamantan-1-ylmethyl)-3-(3-chloro-2-fluorophenyl)urea

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 25℃; for 12h;	85%

3-(4-chloro-3-nitrophenyl)-3-fluoro-2-benzofuran-1(3H)-one + 3-chloro-2-fluoroaniline (2106-04-9) → (3-chloro-2-fluorophenyl)-3-(4-chloro-3-nitrophenyl)-3-hydroxy-2,3-dihydro-1H-isoindol-1-one (870605-90-6)

Conditions	Yield
With N,N-dimethyl-aniline In 1,2-dichloro-ethane at 70℃; for 20h;	84%

3-chloro-2-fluoroaniline (2106-04-9) + (R)-4-chloro-7-methoxyquinazolin-6-yl 2,4-dimethylpiperazine-1-carboxylate → (R)-4-((3-chloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl-2,4-dimethylpiperazinyl-1-carboxylic acid ester

Conditions	Yield
In isopropyl alcohol for 3h; Reflux;	83.1%
In isopropyl alcohol for 3h; Reflux;	83.6%

methyl 8-(1-bromoethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxylate (1296271-41-4) + 3-chloro-2-fluoroaniline (2106-04-9) → methyl 8-(1-(3-chloro-2-fluorophenylamino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxylate (1296271-42-5)

Conditions	Yield
In dichloromethane at 20 - 50℃; for 32h;	82%
In dichloromethane at 20 - 50℃; for 32h;	82%

3-chloro-2-fluoroaniline (2106-04-9) + 4(5)formylimidazole (3034-50-2) → (3-chloro-2-fluoro-phenyl)-(3H-imidazol-4-ylmethyl)-amine (1020818-01-2)

Conditions	Yield
Stage #1: 3-chloro-2-fluoroaniline; 4(5)formylimidazole In methanol at 60℃; Stage #2: With sodium tetrahydroborate In methanol at 20℃; for 4h; Stage #3: With water In methanol	81%

3,4-dihydro-4-oxo-6-(1,4-dioxa-spiro[4,5]decan-8-yl-oxy)-7-methoxy-quinazoline (1046452-66-7) + 3-chloro-2-fluoroaniline (2106-04-9) → 4-[(3-chloro-2-fluoro-phenyl)amino]-6-(4-oxo-cyclohexyloxy)-7-methoxy-quinazoline (1046137-42-1)

Conditions	Yield
Stage #1: 3,4-dihydro-4-oxo-6-(1,4-dioxa-spiro[4,5]decan-8-yl-oxy)-7-methoxy-quinazoline With triethylamine; trichlorophosphate In acetonitrile at 40℃; for 2h; Reflux; Stage #2: 3-chloro-2-fluoroaniline With triethylamine at 20 - 40℃; for 5h; Reflux; Stage #3: With hydrogenchloride; sodium hydroxide In dichloromethane; water; isopropyl alcohol	80%
Stage #1: 3,4-dihydro-4-oxo-6-(1,4-dioxa-spiro[4,5]decan-8-yl-oxy)-7-methoxy-quinazoline With triethylamine; trichlorophosphate In acetonitrile at 40℃; for 2h; Inert atmosphere; Reflux; Stage #2: 3-chloro-2-fluoroaniline With triethylamine In acetonitrile at 20 - 40℃; Inert atmosphere; Stage #3: With hydrogenchloride In water; isopropyl alcohol at 20℃;	73%

(2S,4S)-4-(4-chloro-quinazolin-7-yloxy)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (849345-43-3) + 3-chloro-2-fluoroaniline (2106-04-9) → methyl (4S)-4-({4-[(3-chloro-2-fluorophenyl)amino]quinazolin-7-yl}oxy)-L-prolinate (849345-44-4)

Conditions	Yield
Stage #1: (2S,4S)-4-(4-chloro-quinazolin-7-yloxy)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester; 3-chloro-2-fluoroaniline With hydrogenchloride In 1,4-dioxane; acetonitrile for 2h; Heating / reflux; Stage #2: With ammonia In methanol	79%

3-chloro-2-fluoroaniline (2106-04-9) + potassium thioacyanate (333-20-0) + 3,4,5-Trimethoxybenzoyl chloride (4521-61-3) + 3-chloropentane-2,4-dione (1694-29-7) → 2-(3,4,5-trimethoxybenzoylimino)-3-(3-chloro-2-fluorophenyl)-4-methyl-5-acetyl-1,3-thiazoline

Conditions	Yield
Stage #1: potassium thioacyanate; 3,4,5-Trimethoxybenzoyl chloride In acetonitrile Stage #2: 3-chloro-2-fluoroaniline; 3-chloropentane-2,4-dione With 1-methyl-1H-imidazole In acetonitrile at 70 - 80℃; for 1h;	76%

2-hydroxy-4-(2-methoxyethoxy)benzoic acid (761455-13-4) + 3-chloro-2-fluoroaniline (2106-04-9) + 1,1'-carbonyldiimidazole (530-62-1) → N-(3-chloro-2-fluorobenzyl)-2-hydroxy-4-(2-methoxyethoxy)benzamide

Conditions	Yield
Stage #1: 2-hydroxy-4-(2-methoxyethoxy)benzoic acid; 1,1'-carbonyldiimidazole In tetrahydrofuran at 20℃; for 0.166667h; Inert atmosphere; Stage #2: 3-chloro-2-fluoroaniline In tetrahydrofuran at 80℃; Inert atmosphere;	76%

3-chloro-2-fluoroaniline (2106-04-9) + (E)-N'-(2-cyano-4-nitrophenyl)-N,N'-dimethylformimidamide → N-(2-fluoro-3-chlorophenyl)-6-nitroquinazolin-4-amine (1290545-22-0)

Conditions	Yield
With acetic acid for 1h; Reflux;	75%

Upstream product

• 3209-22-1 1,2-Dichloro-3-nitrobenzene 
• 2106-49-2 1-chloro-2-fluoro-3-nitrobenzene 

Downstream Products

• 2317-75-1 ethyl (3-chloro-2-fluorophenyl)carbamate 
• 2794-55-0 N-<2-Fluor3-chlor-phenyl>-carbamidsaeureisopropylester 
• 833451-52-8 6-chloro-N₄-(3-chloro-2-fluorophenyl)pyrimidine-4,5-diamine 
• 612501-52-7 4-(3-chloro-2-fluoroanilino)-6-hydroxy-7-methoxyquinazoline 
• 850083-43-1 1-methyl-4-(3-chloro-2-fluorophenylamino)piperidine 
• 873697-68-8 3-amino-2-fluorobenzonitrile 
• 127142-65-8 1-chloro-2-fluoro-3-isothiocyanatobenzene 
• 144584-65-6 1-bromo-2-fluoro-3-chlorobenzene 
• 757247-98-6 4-amino-2-chloro-3-fluoro-benzaldehyde 
• 1202228-88-3 C₁₄H₈ClF₂N₃ 
• 115843-99-7 4-bromo-3-chloro-2-fluoroaniline 
• 1272719-26-2 C₈H₂ClFN₂S 
• 1272718-97-4 4-[7-(3-chloro-4-cyano-2-fluoro-phenyl)-8-oxo-6-thioxo-5,7-diaza-spiro[3.4]oct-5-yl]-2-fluoro-N-methyl-benzamide 
• 1272718-99-6 4-[3-(3-chloro-4-cyano-2-fluoro-phenyl)-5,5-dimethyl-4-oxo-2-thioxo-imidazolidin-1-yl]-2-fluoro-N-methyl-benzamide 

Relevant articles and documents

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