53145-38-3

Basic information

• Product Name: 2-Chloro-6-fluoroanisole
• Synonyms: 1-Chloro-3-fluoro-2-Methoxybenzene;1-Chloro-3-fluoro-2-methoxybenzene, 2-Chloro-6-fluorophenyl methyl ether
• CAS NO: 53145-38-3
• Molecular Formula: C₇H₆ClFO
• Molecular Weight: 160.58
• Mol File: 53145-38-3.mol
• Article Data: 2

Chemical Properties

• Boiling Point: 186.4 °C at 760 mmHg
• Flash Point: 66.5 °C
• Appearance: /
• Density: 1.239 g/cm³
• Vapor Pressure: 0.913mmHg at 25°C
• Refractive Index: 1.495
• Storage Temp.: Sealed in dry,Room Temperature
• CAS DataBase Reference: 2-Chloro-6-fluoroanisole(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Chloro-6-fluoroanisole(53145-38-3)
• EPA Substance Registry System: 2-Chloro-6-fluoroanisole(53145-38-3)

Safety Data

• Hazard Codes: Xi
• HazardClass: IRRITANT
• PackingGroup: III
• Hazardous Substances Data: 53145-38-3(Hazardous Substances Data)

Usage

Chemical Properties

Colorless liquid

InChI:InChI=1/C7H6ClFO/c1-10-7-5(8)3-2-4-6(7)9/h2-4H,1H3

Synthetic route

2-chloro-6-fluorophenol (2040-90-6) + methyl iodide (74-88-4) → 1-chloro-3-fluoro-2-methoxybenzene (53145-38-3)

Conditions	Yield
With potassium carbonate In tetrahydrofuran at 20℃; for 3h;	94%

1,2-Dichloro-3-nitrobenzene (3209-22-1) → 1-chloro-3-fluoro-2-methoxybenzene (53145-38-3)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: diisopropylamine / methanol / 5 h / 60 °C 2.1: hydrogen; 1% platinum on charcoal / toluene / 18 h / 40 °C / 3375.34 Torr / Autoclave 3.1: hydrogenchloride / water / 0.5 h / 50 °C 3.2: 2 h / 0 °C 3.3: 1 h View Scheme

3-chloro-2-methoxyaniline (51114-68-2) → 1-chloro-3-fluoro-2-methoxybenzene (53145-38-3)

Conditions	Yield
Stage #1: 3-chloro-2-methoxyaniline With hydrogenchloride In water at 50℃; for 0.5h; Stage #2: With sodium nitrite In water at 0℃; for 2h; Stage #3: With tetrafluoroboric acid In water for 1h; Temperature; Reagent/catalyst;	26 g

1-chloro-3-fluoro-2-methoxybenzene (53145-38-3) → (4-chloro-2-fluoro-3-methoxy-phenyl)boronic acid (944129-07-1)

Conditions	Yield
Stage #1: 1-chloro-3-fluoro-2-methoxybenzene With n-butyllithium In 1,2-dimethoxyethane at -78 - -70.1℃; for 1.75h; Stage #2: With Trimethyl borate In 1,2-dimethoxyethane at -67 - 20℃; Time; Temperature; Further stages;	93%
Multi-step reaction with 2 steps 1.1: n-butyllithium / 1,2-dimethoxyethane; hexane / 1.75 h / -77 - -70.1 °C / Inert atmosphere 1.2: 1.37 h / -74.1 - 23.1 °C 2.1: potassium hydroxide; water / 1,2-dimethoxyethane / 2 h / 30 °C / Cooling View Scheme

Trimethyl borate (121-43-7) + 1-chloro-3-fluoro-2-methoxybenzene (53145-38-3) → (4-chloro-2-fluoro-3-methoxy-phenyl)boronic acid (944129-07-1)

Conditions	Yield
With n-butyllithium In tetrahydrofuran; hexane; cyclohexane at -50℃; Flow reactor;	92%
Stage #1: 1-chloro-3-fluoro-2-methoxybenzene With n-butyllithium In 1,2-dimethoxyethane at -65℃; Inert atmosphere; Stage #2: Trimethyl borate In 1,2-dimethoxyethane at -65 - 30℃; Time; Inert atmosphere;

2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (61676-62-8) + 1-chloro-3-fluoro-2-methoxybenzene (53145-38-3) → 2-(4-chloro-2-fluoro-3-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1126321-06-9)

Conditions	Yield
With n-butyllithium In tetrahydrofuran; hexane; cyclohexane at -50℃; Flow reactor;	92%

N,N-dimethyl-formamide (68-12-2, 33513-42-7) + 1-chloro-3-fluoro-2-methoxybenzene (53145-38-3) → 4-chloro-2-fluoro-3-methoxybenzaldehyde (1002344-97-9)

Conditions	Yield
With n-butyllithium In tetrahydrofuran; hexane; cyclohexane at -50℃; Flow reactor;	88%

1-chloro-3-fluoro-2-methoxybenzene (53145-38-3) → 5-[(3R)-3-(3-chloro-2-methoxyphenoxy)pyrrolidin-1-yl]-5-methyl-2,2-diphenylhexanenitrile

Conditions	Yield
Stage #1: 5-[(3R)-3-hydroxypyrrolidin-1-yl]-5-methyl-2,2-diphenylhexanenitrile With sodium hydride In N,N-dimethyl-formamide at 0℃; for 1h; Stage #2: 1-chloro-3-fluoro-2-methoxybenzene In N,N-dimethyl-formamide at 60℃; for 96h; Stage #3: With water In ethyl acetate; N,N-dimethyl-formamide	74%

chloroacetyl chloride (79-04-9) + 1-chloro-3-fluoro-2-methoxybenzene (53145-38-3) → C9H7Cl2FO2

Conditions	Yield
Stage #1: 1-chloro-3-fluoro-2-methoxybenzene With n-hexyllithium In tetrahydrofuran; hexane at -60℃; for 1h; Stage #2: With zinc(II) chloride In tetrahydrofuran; hexane at -60 - -10℃; Stage #3: chloroacetyl chloride; copper(l) chloride In tetrahydrofuran; hexane at -10 - 20℃; Further stages.;	71%

Benzyloxyacetyl chloride (19810-31-2) + 1-chloro-3-fluoro-2-methoxybenzene (53145-38-3) → C16H14ClFO3

Conditions	Yield
Stage #1: 1-chloro-3-fluoro-2-methoxybenzene With n-hexyllithium In tetrahydrofuran; hexane at -60℃; for 1h; Stage #2: With zinc(II) chloride In tetrahydrofuran; hexane at -60 - -10℃; Stage #3: Benzyloxyacetyl chloride; copper(l) chloride In tetrahydrofuran; hexane at -10 - 20℃; Further stages.;	70%

carbon dioxide (124-38-9) + 1-chloro-3-fluoro-2-methoxybenzene (53145-38-3) → 4-chloro-2-fluoro-3-methoxybenzoic acid (1169870-80-7)

Conditions	Yield
With n-butyllithium In tetrahydrofuran; hexane; cyclohexane at -50℃; Flow reactor;	64%

1-chloro-3-fluoro-2-methoxybenzene (53145-38-3) + 2-anilineboronic acid pinacol ester (191171-55-8) → C13H12FNO

Conditions	Yield
With allylchloro[1,3-bis(2,6-di-isopropylphenyl)imidazol-2-ylidene]palladium(II); barium(II) hydroxide In isopropyl alcohol at 80℃; for 6h;	63%

methyl 4-methoxypicolinate (29681-43-4) + phenyl chloroformate (1885-14-9) + 1-chloro-3-fluoro-2-methoxybenzene (53145-38-3) → 6-(4-chloro-2-fluoro-3-methoxyphenyl)-4-oxo-5,6-dihydro-4H-pyridine-1,2-dicarboxylic acid 2-methyl ester 1-phenyl ester (1257337-12-4)

Conditions	Yield
Stage #1: 1-chloro-3-fluoro-2-methoxybenzene With n-butyllithium In tetrahydrofuran; hexane at -60 - -48℃; for 1h; Inert atmosphere; Stage #2: With zinc(II) chloride In tetrahydrofuran; hexane at -45℃; for 2.5h; Stage #3: methyl 4-methoxypicolinate; phenyl chloroformate	57%

1-chloro-3-fluoro-2-methoxybenzene (53145-38-3) → 2-chloro-6-fluorophenol (2040-90-6)

Conditions	Yield
With pyridine hydrochloride
With boron tribromide In dichloromethane at -78 - 20℃; for 16h;

Hexanoyl chloride (142-61-0) + 1-chloro-3-fluoro-2-methoxybenzene (53145-38-3) → 1-(3-chloro-5-fluoro-4-methoxyphenyl)-1-hexanone (371757-70-9) + C12H14O2FCl

Conditions	Yield
With aluminium trichloride In dichloromethane Friedel-Crafts acylation;

1-chloro-3-fluoro-2-methoxybenzene (53145-38-3) → C14H16O2FCl

Conditions	Yield
Multi-step reaction with 2 steps 1: AlCl3 / CH2Cl2 2: K2CO3 View Scheme

1-chloro-3-fluoro-2-methoxybenzene (53145-38-3) → C14H16O2FCl

Conditions	Yield
Multi-step reaction with 2 steps 1.1: AlCl3 / CH2Cl2 2.2: H2SO4 / toluene View Scheme

1-chloro-3-fluoro-2-methoxybenzene (53145-38-3) → α-bis-(2-Fluor-6-chlorphenoxy)essigsaeure (53145-35-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: Py*HCl 2: NaOEt View Scheme

Hexanoyl chloride (142-61-0) + 1-chloro-3-fluoro-2-methoxybenzene (53145-38-3) → 1-(3-chloro-5-fluoro-4-methoxyphenyl)-1-hexanone (371757-70-9)

Conditions	Yield
aluminium trichloride In water

1-chloro-3-fluoro-2-methoxybenzene (53145-38-3) → 6-chloro-2-fluoro-3-lithioanisole

Conditions	Yield
With n-butyllithium In 1,2-dimethoxyethane; hexane at -70 - -50℃; for 0.333333h; Product distribution / selectivity; Cooling with dry ice bath;
With n-butyllithium In tetrahydrofuran; hexane at -70 - -48℃; for 0.75h; Product distribution / selectivity;
With n-butyllithium In hexanes; 1,2-dimethoxyethane at -70 - -55℃; for 1.5h; Product distribution / selectivity;
With n-butyllithium In hexanes; 1,2-dimethoxyethane at -73.4 - -65℃; for 1.90333 - 4.48333h; Product distribution / selectivity; Cooling with acetone-dry ice;
With n-butyllithium In 1,2-dimethoxyethane; hexane at -72℃; for 2.01667h; Cooling with acetone-dry ice;

1-chloro-3-fluoro-2-methoxybenzene (53145-38-3) + zinc(II) chloride (7646-85-7) → (4-chloro-2-fluoro-3-methoxyphenyl)zinc(II) chloride (1257337-33-9)

Conditions	Yield
Stage #1: 1-chloro-3-fluoro-2-methoxybenzene With n-butyllithium In tetrahydrofuran; hexane at -60 - -48℃; for 1h; Inert atmosphere; Stage #2: zinc(II) chloride In tetrahydrofuran; hexane at -60 - -45℃; for 2.5h; Inert atmosphere;

Trimethyl borate (121-43-7) + 1-chloro-3-fluoro-2-methoxybenzene (53145-38-3) → 4-chloro-2-fluoro-3-methoxyphenyl dimethylboronate (1426539-30-1)

Conditions	Yield
With n-butyllithium In 1,2-dimethoxyethane; hexane for 0.616667h; Molecular sieve;
Stage #1: 1-chloro-3-fluoro-2-methoxybenzene With n-butyllithium In 1,2-dimethoxyethane; hexane at -77 - -70.1℃; for 1.75h; Inert atmosphere; Stage #2: Trimethyl borate In 1,2-dimethoxyethane; hexane at -74.1 - 23.1℃; for 1.36667h;

1-chloro-3-fluoro-2-methoxybenzene (53145-38-3) → 4,3'-dichloro-2-fluoro-3,2'-dimethoxybiphenyl (1426539-35-6)

Conditions	Yield
Stage #1: 1-chloro-3-fluoro-2-methoxybenzene With n-butyllithium In 1,2-dimethoxyethane; hexane at -70℃; Molecular sieve; Inert atmosphere; Stage #2: at -48 - 1℃; Inert atmosphere;

1-chloro-3-fluoro-2-methoxybenzene (53145-38-3) → halauxifen methyl ester

Conditions	Yield
Multi-step reaction with 3 steps 1.1: n-butyllithium / 1,2-dimethoxyethane / -65 °C / Inert atmosphere 1.2: -65 - 30 °C / Inert atmosphere 2.1: palladium diacetate; triphenylphosphine / 1,2-dimethoxyethane; acetonitrile / Inert atmosphere 2.2: 2.5 h / 50 °C 3.1: acetyl chloride / methanol / 7 h / 50 °C / Inert atmosphere View Scheme

1-chloro-3-fluoro-2-methoxybenzene (53145-38-3) → methyl 4-(acetylamino)-3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)pyridine-2-carboxylate (943831-44-5)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: n-butyllithium / 1,2-dimethoxyethane / -65 °C / Inert atmosphere 1.2: -65 - 30 °C / Inert atmosphere 2.1: palladium diacetate; triphenylphosphine / 1,2-dimethoxyethane; acetonitrile / Inert atmosphere 2.2: 2.5 h / 50 °C View Scheme
Multi-step reaction with 3 steps 1: n-butyllithium / 1,2-dimethoxyethane; hexane / 2.02 h / -72 °C / Cooling with acetone-dry ice 2: 1,2-dimethoxyethane; hexane / -72 °C / Cooling with acetone-dry ice 3: palladium diacetate; potassium carbonate; triphenylphosphine; tetrabutylammomium bromide / toluene; acetonitrile; water / 2 h / 65 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1.1: n-butyllithium / 1,2-dimethoxyethane; hexane / 1.75 h / -77 - -70.1 °C / Inert atmosphere 1.2: 1.37 h / -74.1 - 23.1 °C 2.1: potassium hydroxide; water / 1,2-dimethoxyethane / 2 h / 30 °C / Cooling 3.1: ethyl acetate / 2 h / 23.1 °C / Inert atmosphere 4.1: triphenylphosphine; palladium diacetate / acetonitrile / 0.08 h / Inert atmosphere 4.2: 2 h / 60 °C / Inert atmosphere View Scheme

1-chloro-3-fluoro-2-methoxybenzene (53145-38-3) → 4-chloro-2-fluoro-3-methoxyphenyl dimethylboronate (1426539-30-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: n-butyllithium / 1,2-dimethoxyethane; hexane / 2.02 h / -72 °C / Cooling with acetone-dry ice 2: 1,2-dimethoxyethane; hexane / -72 °C / Cooling with acetone-dry ice View Scheme

1-chloro-3-fluoro-2-methoxybenzene (53145-38-3) → 2-(4-chloro-2-fluoro-3-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1126321-06-9)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: n-butyllithium / 1,2-dimethoxyethane; hexane / 1.75 h / -77 - -70.1 °C / Inert atmosphere 1.2: 1.37 h / -74.1 - 23.1 °C 2.1: potassium hydroxide; water / 1,2-dimethoxyethane / 2 h / 30 °C / Cooling 3.1: ethyl acetate / 2 h / 23.1 °C / Inert atmosphere View Scheme

N-fluorobis(benzenesulfon)imide (133745-75-2) + 1-chloro-3-fluoro-2-methoxybenzene (53145-38-3) → N-(3-chloro-5-fluoro-4-methoxyphenyl)-N-(phenylsulfonyl)benzenesulfonamide (1453101-06-8) + C19H15ClFNO5S2 (1453101-26-2)

Conditions	Yield
With [Ag(2,2'-bipyridine)2](ClO4); C20H28N4O2Pd*2CHF3O3S In acetonitrile at 23℃; for 24h; Inert atmosphere; Sealed tube; Overall yield = 78 %; Overall yield = 106.7 mg;

N-fluorobis(benzenesulfon)imide (133745-75-2) + 1-chloro-3-fluoro-2-methoxybenzene (53145-38-3) → N-(3-chloro-5-fluoro-4-methoxyphenyl)-N-(phenylsulfonyl)benzenesulfonamide (1453101-06-8) + C19H15ClFNO5S2 (1453101-26-2) + C19H15ClFNO5S2

Conditions	Yield
With [Ag(2,2'-bipyridine)2](ClO4); C20H28N4O2Pd(2+)*2CF3O3S(1-) In acetonitrile at 23℃; for 24h; Inert atmosphere; Sealed tube; Overall yield = 78 %; Overall yield = 106.7 mg;

1-chloro-3-fluoro-2-methoxybenzene (53145-38-3) → C31H32FNO2

Conditions	Yield
Multi-step reaction with 2 steps 1: allylchloro[1,3-bis(2,6-di-isopropylphenyl)imidazol-2-ylidene]palladium(II); barium(II) hydroxide / isopropyl alcohol / 6 h / 80 °C 2: Amberlyst 15(H) / toluene / 6 h / Dean-Stark; Reflux View Scheme

Upstream product

• 2040-90-6 2-chloro-6-fluorophenol 
• 74-88-4 methyl iodide 
• 3209-22-1 1,2-Dichloro-3-nitrobenzene 
• 51114-68-2 3-chloro-2-methoxyaniline 

Downstream Products

• 1453101-06-8 N-(3-chloro-5-fluoro-4-methoxyphenyl)-N-(phenylsulfonyl)benzenesulfonamide 
• 1453101-26-2 C₁₉H₁₅ClFNO₅S₂ 
• 1169870-80-7 4-chloro-2-fluoro-3-methoxybenzoic acid 
• 1002344-97-9 4-chloro-2-fluoro-3-methoxybenzaldehyde 
• 1126321-06-9 2-(4-chloro-2-fluoro-3-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 
• 1426539-30-1 4-chloro-2-fluoro-3-methoxyphenyl dimethylboronate 
• 944129-07-1 (4-chloro-2-fluoro-3-methoxyphenyl)-boronic acid 
• 943831-44-5 methyl 4-(acetylamino)-3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)pyridine-2-carboxylate 
• 943831-98-9 halauxifen methyl ester 
• 1257337-33-9 (4-chloro-2-fluoro-3-methoxyphenyl)zinc(II) chloride 
• 1257337-12-4 6-(4-chloro-2-fluoro-3-methoxyphenyl)-4-oxo-5,6-dihydro-4H-pyridine-1,2-dicarboxylic acid 2-methyl ester 1-phenyl ester 
• 371757-70-9 1-(3-chloro-5-fluoro-4-methoxyphenyl)-1-hexanone 
• 53145-35-0 α-bis-(2-Fluor-6-chlorphenoxy)essigsaeure 
• 2040-90-6 2-chloro-6-fluorophenol 

Relevant articles and documents

A 2-chloro-6-fluoro anisole and wherein the intermediate preparation method

The invention discloses a method for preparing 2-chlorine-6-fluoroanisole and midbodies of the 2-chlorine-6-fluoroanisole. The method for preparing the 2-chlorine-6-fluoroanisole comprises the following step that under the condition that the temperature ranges from 100 DEG C to 150 DEG C, a cleavage reaction is conducted on a compound shown as the formula V. A method for preparing a compound shown as the formula III comprises the following step that in a solvent and under catalysis of platinum carbon, a reduction reaction is conducted on a compound shown as the formula II and hydrogen, so that the compound shown as the formula III is obtained. A method for preparing the compound shown as the formula II comprises the following step that in a solvent and under catalysis of a catalyst, an etherification reaction is conducted on a compound shown as the formula I and sodium methylate, so that the compound shown as the formula II is obtained. According to the method for preparing the 2-chlorine-6-fluoroanisole, raw materials are low in price and easy to obtain, the production cost is low, reaction conditions are gentle, the yield is high, and the method is suitable for industrialized production.