399-95-1

Basic information

• Product Name: 4-Amino-3-fluorophenol
• Synonyms: 4-AMINO-3-FLUOROPHENOL;3-FLUORO-4-AMINOPHENOL;BUTTPARK 33\04-79;IFLAB-BB F2108-0045;Aminofluorophenol3;4-Amino-3-Fluorophenol 3-Fluoro-4-Aminophenol;2-FLUORO-4-YDROXYANILINE;4-Amino-3-fluorophenol 98%
• CAS NO: 399-95-1
• Molecular Formula: C₆H₆FNO
• Molecular Weight: 127.12
• EINECS: 402-230-0
• Product Categories: Aromatic Phenols;Phenol&Thiophenol&Mercaptan;Amines;Aromatics;Miscellaneous Reagents
• Mol File: 399-95-1.mol
• Article Data: 37

Chemical Properties

• Melting Point: 135-137°C
• Boiling Point: 263.3 °C at 760 mmHg
• Flash Point: 113.1 °C
• Appearance: /
• Density: 1.347 g/cm³
• Vapor Pressure: 0.00633mmHg at 25°C
• Refractive Index: 1.601
• Storage Temp.: Refrigerator
• PKA: 9.23±0.18(Predicted)
• CAS DataBase Reference: 4-Amino-3-fluorophenol(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Amino-3-fluorophenol(399-95-1)
• EPA Substance Registry System: 4-Amino-3-fluorophenol(399-95-1)

Safety Data

• Hazard Codes: T,Xi,N
• Statements: 22-43-45-51/53
• Safety Statements: 45-53-61
• RIDADR: 3077
• HazardClass: 9
• PackingGroup: III
• Hazardous Substances Data: 399-95-1(Hazardous Substances Data)

Usage

Chemical Properties

Dark Brown Solid

InChI:InChI=1/C6H6FNO/c7-5-3-4(8)1-2-6(5)9/h1-3,9H,8H2

Synthetic route

3-fluoro-4-nitrophenol (394-41-2) → 4-amino-3-fluorophenol (399-95-1)

Conditions	Yield
With hydrogen; palladium 10% on activated carbon In tetrahydrofuran; ethanol at 20℃; for 4.5h;	100%
With iron; acetic acid In ethyl acetate for 3h; Heating / reflux;	98%
With hydrogen; palladium 10% on activated carbon In ethyl acetate for 4h;	97%

N-(2-fluoro-4-hydroxyphenyl)acetamide (103842-00-8) → 4-amino-3-fluorophenol (399-95-1)

Conditions	Yield
With hydrogenchloride In water at 80℃; Inert atmosphere;	88%

aluminium hydride (7784-21-6) + sodium hydrogencarbonate (144-55-8) + ortho-nitrofluorobenzene (1493-27-2) → 4-amino-3-fluorophenol (399-95-1)

Conditions	Yield
With sulfuric acid In water	86%
With sulfuric acid In water	86%

ortho-nitrofluorobenzene (1493-27-2) → 4-amino-3-fluorophenol (399-95-1)

Conditions	Yield
With oxalic acid; aluminium In water at 80 - 85℃; for 1.5h;	40.7%
With sulfuric acid at 90℃; (electrochemical reduction);

3-fluoro-4-phenylazo-phenol (326-18-1) → 4-amino-3-fluorophenol (399-95-1)

Conditions	Yield
With sodium dithionite; water

O-(3-fluorophenyl)hydroxylamine (127682-43-3) → 3-fluorophenol (372-20-3) + 4-amino-3-fluorophenol (399-95-1) + 2-amino-5-fluorophenol (53981-24-1) + 2-amino-3-fluorophenol (53981-23-0)

Conditions	Yield
With trifluoroacetic acid at 70℃; for 6h; Product distribution; Rate constant; Kinetics; ΔH(excit.), ΔG(excit.), ΔS(excit.);

3-fluorophenol (372-20-3) → 4-amino-3-fluorophenol (399-95-1)

Conditions	Yield
Multi-step reaction with 2 steps 2: sodium dithionite; water View Scheme
Multi-step reaction with 2 steps 1: nitric acid / water / 0.5 h / 8 - 10 °C / Cooling with ice 2: sodium sulfide / 0.08 h / Microwave irradiation; Ionic liquid View Scheme

3-fluoro-4-nitrophenol (394-41-2) + iron (7439-89-6) → 4-amino-3-fluorophenol (399-95-1)

Conditions	Yield
In water; acetic acid

2-fluoro-4-hydroxyaniline hydrochloride (18266-53-0) → 4-amino-3-fluorophenol (399-95-1)

Conditions	Yield
With sodium hydroxide In methanol; water

C6H4FN2 → 4-amino-3-fluorophenol (399-95-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: copper(II) sulfate; sulfuric acid; water / 100 °C 2: nitric acid / water / 0.5 h / 8 - 10 °C / Cooling with ice 3: sodium sulfide / 0.08 h / Microwave irradiation; Ionic liquid View Scheme

meta-fluoroaniline (372-19-0) → 4-amino-3-fluorophenol (399-95-1)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: sodium nitrite / 1 h / Cooling with ice; Ionic liquid 1.2: 1 h 2.1: copper(II) sulfate; sulfuric acid; water / 100 °C 3.1: nitric acid / water / 0.5 h / 8 - 10 °C / Cooling with ice 4.1: sodium sulfide / 0.08 h / Microwave irradiation; Ionic liquid View Scheme

2,4-Difluoronitrobenzene (446-35-5) → 4-amino-3-fluorophenol (399-95-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium methylate / 5.5 h / 45 °C / Inert atmosphere 2: benzene; aluminum (III) chloride / 11 h / 45 °C 3: nickel(II) nitrate; palladium dichloride; tetrabutoxytitanium; hydrogen / ethanol / 2 h / 45 °C / 1500.15 Torr View Scheme

4-amino-3-fluorophenol (399-95-1) + acetic anhydride (108-24-7) → N-(2-fluoro-4-hydroxyphenyl)acetamide (103842-00-8)

Conditions	Yield
Stage #1: 4-amino-3-fluorophenol; acetic anhydride With acetic acid at 20℃; for 2h; Stage #2: With water at 20℃; for 0.5h;	100%
In 1,2-dichloro-ethane at 10 - 20℃; for 2.5h;	95.8%
In water	66%
In water	66%

4-amino-3-fluorophenol (399-95-1) + bis-(2-chloroethyl)amine hydrochloride (821-48-7) → 3-fluoro-4-(piperazin-1-yl)phenol hydrochloride

Conditions	Yield
In sulfolane at 150℃; for 16h;	98%

4-bromo-pyridine-2-carboxylic acid methyl amide (1209459-88-0) + 4-amino-3-fluorophenol (399-95-1) → 4-(4-amino-3-fluorophenoxy)pyridine-2-carboxylic acid methyl amide (757251-39-1)

Conditions	Yield
With N-benzyl-N,N,N-triethylammonium chloride; potassium iodide; sodium hydroxide In water at 30 - 70℃; for 2h; Reagent/catalyst;	97.5%

N-(6-methoxybenzo[d]thiazol-2-yl)-1H-imidazole-1-carboxamide (945404-21-7) + 4-amino-3-fluorophenol (399-95-1) → 1-(2-fluoro-4-hydroxyphenyl)-3-(6-methoxybenzo[d]thiazol-2-yl)urea

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 20℃;	97%

4-amino-3-fluorophenol (399-95-1) + 4-chloro-N-methylpicolinamide (220000-87-3) → 4-(4-amino-3-fluorophenoxy)pyridine-2-carboxylic acid methyl amide (757251-39-1)

Conditions	Yield
With potassium carbonate In 1,2-dichloro-ethane for 4h; Reflux;	96.3%
Stage #1: 4-amino-3-fluorophenol With potassium tert-butylate In tetrahydrofuran at 20 - 30℃; for 2h; Stage #2: 4-chloro-N-methylpicolinamide In tetrahydrofuran Reagent/catalyst; Solvent; Temperature; Reflux;	94%
Stage #1: 4-amino-3-fluorophenol With potassium tert-butylate In dimethyl amine at 20℃; for 2h; Inert atmosphere; Stage #2: 4-chloro-N-methylpicolinamide With potassium carbonate In dimethyl amine at 85℃; Time; Inert atmosphere;	92%

4-amino-3-fluorophenol (399-95-1) + tert-butyldimethylsilyl chloride (18162-48-6) → 4-((tert-butyldimethylsilyl)oxy)-2-fluoroaniline

Conditions	Yield
With 1H-imidazole In tetrahydrofuran at 20℃; for 12h;	95%

C11H7ClN4OS (1353531-00-6) + 4-amino-3-fluorophenol (399-95-1) → 1-(6-chlorobenzo[d]thiazol-2-yl)-3-(2-fluoro-4-hydroxyphenyl)urea

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 20℃;	94%

methyl 4-formyl-2-methyl-benzoate (74733-23-6) + 4-amino-3-fluorophenol (399-95-1) → 4-[(2-fluoro-4-hydroxy-phenylamino)-methyl]-2-methyl-benzoic acid methyl ester

Conditions	Yield
Stage #1: methyl 4-formyl-2-methyl-benzoate; 4-amino-3-fluorophenol With acetic acid at 20℃; for 2h; Stage #2: With sodium tris(acetoxy)borohydride at 20℃; Stage #3: With water; sodium hydrogencarbonate In ethyl acetate	93%

1H-indol-2-ylcarboxaldehyde (19005-93-7) + 2-Butynoic acid (590-93-2) + 1,1,3,3-tetramethylbutane isonitrile (14542-93-9) + 4-amino-3-fluorophenol (399-95-1) → N-(1-(1H-indol-2-yl)-2-oxo-2-((2,4,4-trimethylpentan-2-yl)amino)ethyl)-N-(2-fluoro-4-hydroxyphenyl)but-2-ynamide

Conditions	Yield
With sodium sulfate In methanol at 20℃; Ugi Condensation;	93%

4-amino-3-fluorophenol (399-95-1) + benzyl chloroformate (501-53-1) → benzyl (2-fluoro-4-hydroxyphenyl)carbamate (1195781-24-8)

Conditions	Yield
With sodium hydrogencarbonate In tetrahydrofuran; water at 20℃;	92%

4-amino-3-fluorophenol (399-95-1) + 2,4-Dimethoxybenzaldehyde (613-45-6) → 4-[(2,4-dimethoxybenzyl)amino]-3-fluorophenol

Conditions	Yield
With sodium tris(acetoxy)borohydride; acetic acid In tetrahydrofuran at 20℃; for 5h;	92%
With sodium tris(acetoxy)borohydride; acetic acid In tetrahydrofuran at 20℃; for 5h;	92%

C15H22ClN3O3 (1431703-16-0) + 4-amino-3-fluorophenol (399-95-1) → C21H27FN4O4

Conditions	Yield
With potassium tert-butylate In N,N-dimethyl acetamide at 100℃; for 16h;	92%

4-amino-3-fluorophenol (399-95-1) + 4-chloro-2-pyridinecarboxamide hydrochloride → 4-(4-amino-3-fluorophenoxy)pyridine-2-carboxylic acid methyl amide (757251-39-1)

Conditions	Yield
Stage #1: 4-amino-3-fluorophenol With copper(l) iodide at 85℃; Stage #2: 4-chloro-2-pyridinecarboxamide hydrochloride for 6h; Temperature; Reagent/catalyst;	91.1%

di-tert-butyl dicarbonate (24424-99-5) + 4-amino-3-fluorophenol (399-95-1) → N-(2-fluoro-4-hydroxyphenyl)carbamic acid tert-butyl ester (911297-02-4)

Conditions	Yield
With indium(III) chloride at 35℃; for 2h;	90%
With indium(III) chloride at 35℃; for 2h; Neat (no solvent);	90%
indium(III) chloride at 35℃; for 2h; Neat (no solvent);	90%

4-amino-3-fluorophenol (399-95-1) + phenyl chloroformate (1885-14-9) → phenyl N-(2-fluoro-4-hydroxyphenyl)carbamate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; for 24h; Cooling with ice;	90%

4-amino-3-fluorophenol (399-95-1) + propionic acid anhydride (123-62-6) → C9H10FNO2

Conditions	Yield
In dichloromethane at 10 - 20℃; for 2.5h;	89.8%

4-chloro-6-methoxy-7-(3-morpholin-4-yl-propoxy)-quinoline (205448-32-4) + 4-amino-3-fluorophenol (399-95-1) → 3-Fluoro-4-{[6-methoxy-7-(3-morpholinopropoxy)-4-quinolyl]oxy}-aniline (479690-10-3)

Conditions	Yield
Stage #1: 4-chloro-6-methoxy-7-(3-morpholin-4-yl-propoxy)-quinoline; 4-amino-3-fluorophenol With sodium t-butanolate In ISOPROPYLAMIDE at 95 - 100℃; for 18h; Industry scale; Stage #2: With aniline; sodium t-butanolate In ISOPROPYLAMIDE at 50 - 100℃; for 18h; Industry scale; Stage #3: With water In ISOPROPYLAMIDE at 20 - 30℃; Industry scale;	89%
With sodium t-butanolate In N,N-dimethyl acetamide at 95 - 100℃; for 36h;

4-amino-3-fluorophenol (399-95-1) + 4-chloro-3-(trifluoromethyl)phenyl isocyanate (327-78-6) → 1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(2-fluoro-4-hydroxyphenyl)urea (1333390-56-9)

Conditions	Yield
In dichloromethane; N,N-dimethyl-formamide at 20℃; for 16h;	89%
In dichloromethane for 6h; Reflux;
In dichloromethane at 20℃; for 16h; Inert atmosphere; Schlenk technique;	401 mg

carbon monoxide (201230-82-2) + 4-amino-3-fluorophenol (399-95-1) + phenylacetylene (536-74-3) → C15H12FNO2

Conditions	Yield
With 1,3-bis-(diphenylphosphino)propane; palladium diacetate; toluene-4-sulfonic acid In tetrahydrofuran; acetonitrile at 120℃; under 23272.3 Torr; for 72h; regioselective reaction;	88%

C22H28ClNO3 (1097210-75-7) + 4-amino-3-fluorophenol (399-95-1) → C28H32ClFN2O3 (1097211-09-0)

Conditions	Yield
Stage #1: C22H28ClNO3 With methanesulfonyl chloride; triethylamine In 1,2-dichloro-ethane at 0 - 25℃; for 2h; Stage #2: 4-amino-3-fluorophenol In 1,2-dichloro-ethane at 85℃; for 12h;	87%

2,4-dichloropyridine (26452-80-2) + 4-amino-3-fluorophenol (399-95-1) → 4-(2-chloro-pyridin-4-yloxy)-2-fluorophenylamine (1041861-97-5)

Conditions	Yield
Stage #1: 4-amino-3-fluorophenol With potassium tert-butylate In ISOPROPYLAMIDE at 20℃; for 0.5h; Stage #2: 2,4-dichloropyridine In ISOPROPYLAMIDE at 80℃; for 12h;	86%
Stage #1: 4-amino-3-fluorophenol With potassium tert-butylate In ISOPROPYLAMIDE at 20℃; for 0.5h; Stage #2: 2,4-dichloropyridine In ISOPROPYLAMIDE at 80℃; for 12h;	86%
Stage #1: 4-amino-3-fluorophenol With potassium tert-butylate In N,N-dimethyl acetamide at 20℃; for 0.5h; Stage #2: 2,4-dichloropyridine In N,N-dimethyl acetamide at 80℃; for 12h;	86%
Stage #1: 4-amino-3-fluorophenol With potassium tert-butylate In N,N-dimethyl acetamide at 20℃; for 0.5h; Stage #2: 2,4-dichloropyridine In N,N-dimethyl acetamide at 85℃; for 4h;	83%

trifluoromethyl trifluorovinyl ether (1187-93-5) + 4-amino-3-fluorophenol (399-95-1) → 2-fluoro-4-[1,1,2-trifluoro-2-(trifluoromethoxy)ethoxy]-aniline (122267-39-4)

Conditions	Yield
With potassium hydroxide In dimethyl sulfoxide; toluene at 0℃; for 3h;	85%

1H-indol-2-ylcarboxaldehyde (19005-93-7) + 2-Butynoic acid (590-93-2) + tert-butylisonitrile (119072-55-8, 7188-38-7) + 4-amino-3-fluorophenol (399-95-1) → N-(2-(tert-butylamino)-1-(1H-indol-2-yl)-2-oxoethyl)-N-(2-fluoro-4-hydroxyphenyl)but-2-ynamide

Conditions	Yield
With sodium sulfate In methanol at 20℃; Ugi Condensation;	85%

3-methoxyphenyl bromide (2398-37-0) + 4-amino-3-fluorophenol (399-95-1) → 4-[(3-methoxyphenyl)amino]-3-fluorophenol (1198117-82-6)

Conditions	Yield
With chloro[2-(dicyclohexylphosphino)-3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl][2-(2-aminoethyl)phenyl]palladium(ll); sodium t-butanolate In 1,4-dioxane at 110℃; for 3h; Inert atmosphere;	84%

4-methyl-1,2,3-thiadiazole-5-yl-formyl isocyanate (1254781-51-5) + 4-amino-3-fluorophenol (399-95-1) → 1-(2-fluoro-4-hydroxyphenyl)-3-[(4-methyl-1,2,3-thiadiazol-5-yl)carbonyl]urea (1417340-65-8)

Conditions	Yield
In 1,2-dichloro-ethane at 20℃; for 8h;	83%
In 1,2-dichloro-ethane at 20℃; for 8.25h;	83%

carbon monoxide (201230-82-2) + 4-amino-3-fluorophenol (399-95-1) + phenylacetylene (536-74-3) → C15H12FNO2

Conditions	Yield
With 5-chloro-2-hydroxybenzoic acid; boric acid; palladium diacetate; 1,2-bis[di(t-butyl)phosphinomethyl]benzene In acetonitrile at 110℃; under 18100.7 Torr; for 48h;	83%

Upstream product

• 1493-27-2 ortho-nitrofluorobenzene 
• 18266-53-0 2-fluoro-4-hydroxyaniline hydrochloride 
• 103842-00-8 N-(2-fluoro-4-hydroxyphenyl)acetamide 
• 372-19-0 meta-fluoroaniline 
• 7784-21-6 aluminium hydride 
• 144-55-8 sodium hydrogencarbonate 
• 394-41-2 3-fluoro-4-nitrophenol 
• 7439-89-6 iron 
• 372-20-3 3-fluorophenol 
• 127682-43-3 O-(3-fluorophenyl)hydroxylamine 
• 326-18-1 3-fluoro-4-phenylazo-phenol 
• 446-35-5 2,4-Difluoronitrobenzene 

Downstream Products

• 122267-39-4 2-fluoro-4-[1,1,2-trifluoro-2-(trifluoromethoxy)ethoxy]-aniline 
• 821765-75-7 N-(2-fluoro-4-hydroxyphenyl)methanesulfonamide 
• 64-17-5 ethanol 
• 869663-76-3 2-fluoro-4-(2-methylpyridin-4-yloxy)phenylamine 
• 1198117-82-6 4-[(3-methoxyphenyl)amino]-3-fluorophenol 
• 1198117-80-4 2-fluoro-4-(3-methoxyphenoxy)aniline 
• 100-66-3 methoxybenzene 
• 1417340-65-8 1-(2-fluoro-4-hydroxyphenyl)-3-[(4-methyl-1,2,3-thiadiazol-5-yl)carbonyl]urea 
• 755037-03-7 regorafenib 
• 122927-84-8 3-fluoro-4-iodophenol 
• 1365658-24-7 4-tert-butyl-N-(2-fluoro-4-hydroxylphenyl)-benzenesulfonamide 

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