70441-63-3

Basic information

• Product Name: 4-FLUORO-N-ISOPROPYLANILINE
• Synonyms: 4-FLUORO-N-ISOPROPYLANILINE;FI-Aniline;FL-ANILINE;4-Fluor-N-(1-methylethyl)-benzenamin;N-(4-Fluorophenyl)isopropylamine;N-(4-Fluorophenyl)-N-isopropylamine;4-Fluoro-N-(1-Methylethyl)benzenaMine
• CAS NO: 70441-63-3
• Molecular Formula: C₉H₁₂FN
• Molecular Weight: 153.2
• Product Categories: Amines;Aromatics;Intermediates
• Mol File: 70441-63-3.mol
• Article Data: 15

Chemical Properties

• Boiling Point: 214℃
• Flash Point: 83℃
• Appearance: /
• Density: 1.045
• Vapor Pressure: 0.161mmHg at 25°C
• Refractive Index: 1.527
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• PKA: 5.91±0.32(Predicted)
• CAS DataBase Reference: 4-FLUORO-N-ISOPROPYLANILINE(CAS DataBase Reference)
• NIST Chemistry Reference: 4-FLUORO-N-ISOPROPYLANILINE(70441-63-3)
• EPA Substance Registry System: 4-FLUORO-N-ISOPROPYLANILINE(70441-63-3)

Safety Data

• RIDADR: 2810
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 70441-63-3(Hazardous Substances Data)

Usage

Uses

4-Fluoro-N-isopropylaniline is an intermediate used in the synthesis of Flufenacet, a herbicide.

InChI:InChI=1/C9H12FN/c1-7(2)11-9-5-3-8(10)4-6-9/h3-7,11H,1-2H3

Synthetic route

4-Fluoronitrobenzene (350-46-9) + acetone (67-64-1) → 4-fluoro-N-isopropyl-aniline (70441-63-3)

Conditions	Yield
With chloroplatinic acid; sodium tetrahydroborate; hydrogen; titanium(IV) oxide In water at 70℃; Temperature; Large scale;	99.2%
With hydrogen at 60℃; under 5250.53 Torr; Autoclave;	93%

4-Fluoronitrobenzene (350-46-9) + 2,2-dimethoxy-propane (77-76-9) → 4-fluoro-N-isopropyl-aniline (70441-63-3)

Conditions	Yield
With 3 % platinum on carbon; hydrogen; toluene-4-sulfonic acid In toluene at 70 - 80℃; under 3750.38 - 15001.5 Torr; for 4h; Reagent/catalyst; Temperature; Pressure; Solvent; Autoclave; Large scale;	98%

4-Fluoronitrobenzene (350-46-9) → 4-fluoro-N-isopropyl-aniline (70441-63-3)

Conditions	Yield
Pt on charcoal In water; acetone; toluene	97%
platinum In acetone

diisopropylamine (108-18-9) + 4-fluoroaniline (371-40-4) → 4-fluoro-N-isopropyl-aniline (70441-63-3)

Conditions	Yield
With μ-diiodo-di((η5-pentamethylcyclopentadienyl)(iodo)iridium) In 5,5-dimethyl-1,3-cyclohexadiene at 155℃; for 10h; Inert atmosphere;	95%

acetone (67-64-1) + 4-fluoroaniline (371-40-4) → 4-fluoro-N-isopropyl-aniline (70441-63-3)

Conditions	Yield
With iridium bromide; formic acid; zinc In water at 30℃; for 20h;	80%
With sodium tetrahydroborate
With sodium tetrahydroborate In neat (no solvent) at 20℃; for 0.5h; Catalytic behavior;	78 %Chromat.

4-fluoroaniline (371-40-4) → 4-fluoro-N-isopropyl-aniline (70441-63-3)

Conditions	Yield
With sodium hydroxide; sodium borohydrid In acetic acid; acetone	71%

N-chloroisopropylamine (26245-56-7) + 4-fluorophenylzinc bromide (181705-93-1) → 4-fluoro-N-isopropyl-aniline (70441-63-3)

Conditions	Yield
With triethylamine In toluene at 0 - 20℃; for 2h; Reagent/catalyst; Inert atmosphere;	58%

(4-fluorophenyl)lithium (1493-23-8) + N-isopropyl-O-(trimethylsilyl)hydroxylamine (219943-31-4) → 4-fluoro-N-isopropyl-aniline (70441-63-3)

Conditions	Yield
With CuCN In tetrahydrofuran at -50 - 20℃; for 2h; Arylation;	45%

isopropyl bromide (75-26-3) + 4-fluoroaniline (371-40-4) → 4-fluoro-N-isopropyl-aniline (70441-63-3)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide for 5h; Reflux;	43%

1-Bromo-4-fluorobenzene (460-00-4) → 4-fluoro-N-isopropyl-aniline (70441-63-3)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: cobalt(II) bromide; trifluoroacetic acid; 3-chloroprop-1-ene / acetonitrile / 0.05 h / 20 °C 1.2: 20 °C 2.1: triethylamine / toluene / 2 h / 0 - 20 °C / Inert atmosphere View Scheme

C12H16FNO2 (1310991-25-3) → 4-fluoro-N-isopropyl-aniline (70441-63-3)

Conditions	Yield
With potassium hydroxide at 130℃; for 2h;	127 mg

chloroacetyl chloride (79-04-9) + 4-fluoro-N-isopropyl-aniline (70441-63-3) → 2-chloro-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide (66602-64-0)

Conditions	Yield
With triethylamine In toluene at 20℃; for 5.5h; Solvent; Temperature;	98%
With pyridine In toluene	97%
With sodium hydroxide	94%
In toluene at 20 - 90℃; for 2h;	93%

tert-butyl-5-((4'-formylbiphenyl-4-yl)ethynyl)-2,2-dimethyl-1,3-dioxan-5-ylcarbamate (1221257-85-7) + 4-fluoro-N-isopropyl-aniline (70441-63-3) → (E)-tert-butyl 4-(4'-(((4-fluorophenyl)(isopropyl)amino)-methyl)biphenyl-4-yl)-1-hydroxy-2-(hydroxymethyl)but-3-en-2-ylcarbamate (1221257-86-8)

Conditions	Yield
With sodium tris(acetoxy)borohydride; acetic acid; N-ethyl-N,N-diisopropylamine In 1,2-dichloro-ethane at 20℃;	94%

bromoacetic acid methyl ester (96-32-2) + 4-fluoro-N-isopropyl-aniline (70441-63-3) → 2-[N-(4-fluorophenyl)-N-isopropylamino]acetate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile for 24h; Inert atmosphere; Reflux;	86%

4-fluoro-N-isopropyl-aniline (70441-63-3) + 4-chloro-1-(2,5-difluoro-phenyl)-5-phenyl-1H-pyrazole-3-carboxylic acid (176232-40-9) → N-(4-fluorophenyl)-N-isopropyl-4-chloro-1-(2,5-difluorophenyl)-5-phenylpyrazole-3-carboxamide

Conditions	Yield
With 2-chloro-1-methyl-pyridinium iodide; triethylamine In dichloromethane for 3h;	84.2%

(2R,3R)-3-bromo-1,2-epoxy-hexane + 4-fluoro-N-isopropyl-aniline (70441-63-3) → 4-fluoro-N-isopropyl-N-(((2R,3S)-3-propyloxirane-2-yl)methyl)aniline

Conditions	Yield
Stage #1: 4-fluoro-N-isopropyl-aniline With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Stage #2: (2R,3R)-3-bromo-1,2-epoxy-hexane In tetrahydrofuran; hexane at -78 - 20℃; for 16h;	31%

2-Bromoacetyl bromide (598-21-0) + 4-fluoro-N-isopropyl-aniline (70441-63-3) → 2-bromo-N-(4-fluoro-phenyl)-N-isopropyl-acetamide (174180-88-2)

Conditions	Yield
With triethylamine In dichloromethane Ambient temperature;

4-fluoro-N-isopropyl-aniline (70441-63-3) + 4-ethylsulfanyl-5-methyl-3-oxo-3H-isoxazole-2-carbonyl chloride (1027241-69-5) → 4-ethylsulfanyl-5-methyl-3-oxo-3H-isoxazole-2-carboxylic acid (4-fluoro-phenyl)-isopropyl-amide

Conditions	Yield
With triethylamine In toluene at 20℃; for 0.583333h; Acylation;

4-fluoro-N-isopropyl-aniline (70441-63-3) → 2-(2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-(4-fluoro-phenyl)-N-isopropyl-acetamide (174180-89-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: Et3N / CH2Cl2 / Ambient temperature 2: 1.) NaH / 1.) DMF, RT, 0.5 h, 2.) DMF, RT, 18 h View Scheme

4-fluoro-N-isopropyl-aniline (70441-63-3) → N-(4-Fluoro-phenyl)-2-[3-(1H-indazol-3-ylmethyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-acetamide

Conditions	Yield
Multi-step reaction with 4 steps 1: Et3N / CH2Cl2 / Ambient temperature 2: 1.) NaH / 1.) DMF, RT, 0.5 h, 2.) DMF, RT, 18 h 3: 1.) NaH, NaN(TMS)2 / 1.) DMF, THF, 0 deg C, 2.) DMF, THF, RT, 2 h 4: 4N aq. HCl / dioxane / 6 h / Ambient temperature View Scheme

4-fluoro-N-isopropyl-aniline (70441-63-3) → 2-[3-(1-tert-butoxycarbonyl-1H-indazol-3-ylmethyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-(4-fluoro-phenyl)-N-isopropyl-acetamide (174180-87-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: Et3N / CH2Cl2 / Ambient temperature 2: 1.) NaH / 1.) DMF, RT, 0.5 h, 2.) DMF, RT, 18 h 3: 1.) NaH, NaN(TMS)2 / 1.) DMF, THF, 0 deg C, 2.) DMF, THF, RT, 2 h View Scheme

4-fluoro-N-isopropyl-aniline (70441-63-3) → 2-[2,4-Dioxo-5-phenyl-3-(3-phenyl-ureido)-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-(4-fluoro-phenyl)-N-isopropyl-acetamide

Conditions	Yield
Multi-step reaction with 2 steps 1: Et3N / CH2Cl2 / Ambient temperature 2: 1.) NaH / 1.) DMF, 30 min, 2.) DMF, RT, 16 h View Scheme

C13H12O4S2 + 4-fluoro-N-isopropyl-aniline (70441-63-3) → 4-(5-(((4-fluorophenyl)(isopropyl)amino)methyl)thiophen-2-yl)benzaldehyde (1220972-78-0)

Conditions	Yield
In toluene Reflux;

4-fluoro-N-isopropyl-aniline (70441-63-3) + Propiolic acid (471-25-0) → C12H12FNO

Conditions	Yield
With dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃;

4-fluoro-N-isopropyl-aniline (70441-63-3) → N-(4-fluorophenyl)-N-isopropyl-3-phenylpropiolamide

Conditions	Yield
Multi-step reaction with 2 steps 1: dicyclohexyl-carbodiimide / dichloromethane / 0 - 20 °C 2: bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine / 3 h / 80 °C / Inert atmosphere View Scheme

4-fluoro-N-isopropyl-aniline (70441-63-3) → N-(4-fluorophenyl)-N-isopropyl-3-(thiophen-2-yl)propiolamide

Conditions	Yield
Multi-step reaction with 2 steps 1: dicyclohexyl-carbodiimide / dichloromethane / 0 - 20 °C 2: bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine / 3 h / 80 °C / Inert atmosphere View Scheme

4-fluoro-N-isopropyl-aniline (70441-63-3) → 3-iodo-1-isopropyl-4-phenyl-1-azaspiro[4.5]deca-3,6,9-triene-2,8-dione

Conditions	Yield
Multi-step reaction with 3 steps 1: dicyclohexyl-carbodiimide / dichloromethane / 0 - 20 °C 2: bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine / 3 h / 80 °C / Inert atmosphere 3: bis-[(trifluoroacetoxy)iodo]benzene; boron trifluoride diethyl etherate / chlorobenzene / 5 h / 80 °C View Scheme

4-fluoro-N-isopropyl-aniline (70441-63-3) → 3-iodo-1-isopropyl-4-(thiophen-2-yl)-1-azaspiro[4.5]deca-3,6,9-triene-2,8-dione

Conditions	Yield
Multi-step reaction with 3 steps 1: dicyclohexyl-carbodiimide / dichloromethane / 0 - 20 °C 2: bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine / 3 h / 80 °C / Inert atmosphere 3: bis-[(trifluoroacetoxy)iodo]benzene; boron trifluoride diethyl etherate / chlorobenzene / 6 h / 80 °C View Scheme

4-fluoro-N-isopropyl-aniline (70441-63-3) → 2-acetoxy-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide

Conditions	Yield
Multi-step reaction with 2 steps 1: toluene / 2 h / 20 - 90 °C 2: toluene / 95 °C View Scheme

4-fluoro-N-isopropyl-aniline (70441-63-3) → N-(4-fluorophenyl)-2-hydroxy-N-(1-methylethyl)acetamide

Conditions	Yield
Multi-step reaction with 3 steps 1: toluene / 2 h / 20 - 90 °C 2: toluene / 95 °C 3: ethanol / 70 °C View Scheme

Upstream product

• 1493-23-8 (4-fluorophenyl)lithium 
• 219943-31-4 N-isopropyl-O-(trimethylsilyl)hydroxylamine 
• 350-46-9 4-Fluoronitrobenzene 
• 67-64-1 acetone 
• 77-76-9 2,2-dimethoxy-propane 
• 1310991-25-3 C₁₂H₁₆FNO₂ 
• 26245-56-7 N-chloroisopropylamine 
• 181705-93-1 4-fluorophenylzinc bromide 
• 460-00-4 1-Bromo-4-fluorobenzene 
• 75-26-3 isopropyl bromide 
• 371-40-4 4-fluoroaniline 
• 108-18-9 diisopropylamine 

Downstream Products

• 1220972-78-0 4-(5-(((4-fluorophenyl)(isopropyl)amino)methyl)thiophen-2-yl)benzaldehyde 
• 54041-17-7 N-(4-fluorophenyl)-2-hydroxy-N-(1-methylethyl)acetamide 
• 142459-58-3 flufenacet 
• 1221257-86-8 (E)-tert-butyl 4-(4'-(((4-fluorophenyl)(isopropyl)amino)-methyl)biphenyl-4-yl)-1-hydroxy-2-(hydroxymethyl)but-3-en-2-ylcarbamate 
• 66602-64-0 2-chloro-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide 
• 174180-87-1 2-[3-(1-tert-butoxycarbonyl-1H-indazol-3-ylmethyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-(4-fluoro-phenyl)-N-isopropyl-acetamide 
• 174180-89-3 2-(2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-(4-fluoro-phenyl)-N-isopropyl-acetamide 
• 174180-88-2 2-bromo-N-(4-fluoro-phenyl)-N-isopropyl-acetamide 

Relevant articles and documents

Synthetic method N - (4 - fluoroaniline) -2 - hydroxyl - N - isopropyl acetamide

The invention belongs to the technical field of medical intermediates, and particularly relates to a synthesis method N - (4 - fluoroaniline) -2 - hydroxyl - N - isopropylacetamide. To the invention, fluoronitrobenzene is used as a starting material, and hydrogenation is carried out. Condensation gives compound A, compound A is coupled to compound B by amide coupling, compound B is subjected to nucleophilic substitution reaction to give compound C, compound C is exchanged through ester exchange to obtain N - (4 - fluoroaniline) -2 - hydroxyl - N - isopropyl acetamide. The synthesis route of the complete N - (4 - fluoroaniline) -2 - hydroxyl - N - isopropyl acetamide is provided, and the synthesized N - (4 - fluoroaniline) -2 - hydroxyl - N - isopropyl acetamide is high in yield and high in purity.

Flufenacet preparation method

The invention discloses a flufenacet preparation method, which comprises synthesis of 2-methylsulfonyl-5-trifluoromethyl-1,3,4-thiadiazole, synthesis of 2-hydroxy-N-(4-fluoroaniline)-N-(1-methylethyl)acetamide and synthesis of 4'-fluoro-N-isopropyl-2-[5-(trifluridine)-1,3,4-thiadiazole-2-imide]acetamide. The optimal flufenacet preparation method is screened by a large number of experiments, the whole process is reasonable in design, particularly the steps of screening optimal reaction conditions and the optimal amount ratio, reaction temperature, reaction time and the like of reaction raw materials, the reaction yield (capable of reaching 90 percent or more) can be greatly increased, side reaction can be reduced, the reaction rate can be increased, the reaction raw materials can be recycled, the production cost is greatly reduced, and a broad application prospect is achieved.

A N-isopropyl-4-fluoro aniline method for the preparation of

The invention discloses an N-isopropyl-4-fluoroaniline preparation method. The preparation method comprises the following steps: adding 1 valent weight of 4-fluoronitrobenzene and 1-5 times of a mole valent weights of a compound (I), adding a transition metal catalyst having a total mass percentage of 0.2-5% and sulfonic acid or carboxylic acid having a total mass percentage of 0.1-10%, and reacting in the presence of an organic solvent in hydrogen environment at 30-130DEG C to obtain N-isopropyl-4-fluoroaniline. The preparation method has the advantages of simple process, high yield and few three wastes, and is benefit for the industrial production.