456-42-8

Basic information

• Product Name: 3-Fluorobenzyl chloride
• Synonyms: 3-Fluorobenzylchloride,97%;3-Benzyl;Benzene, 1-(chloromethyl)-3-fluoro-;à-chloro-3-fluorotoluene;3-Fluorobenzyl chloride 97%;α-Chloro-3-fluorotoluene, 1-Chloromethyl-3-fluorobenzene;3-Fluorobenzyl chloride,96%;α-Chloro-3-fluorotoluene
• CAS NO: 456-42-8
• Molecular Formula: C₇H₆ClF
• Molecular Weight: 144.57
• EINECS: 207-264-8
• Product Categories: Aromatic Halides (substituted)
• Mol File: 456-42-8.mol
• Article Data: 14

Chemical Properties

• Melting Point: 34.5-36 °C
• Boiling Point: 176-177 °C
• Flash Point: 138 °F
• Appearance: Colorless to light yellow liquid
• Density: 1.194 g/mL at 25 °C(lit.)
• Refractive Index: n20/D 1.511(lit.)
• Storage Temp.: Store below +30°C.
• Solubility: 40g/l
• Water Solubility: 40 g/L (20 ºC)
• Sensitive: Lachrymatory
• BRN: 742265
• CAS DataBase Reference: 3-Fluorobenzyl chloride(CAS DataBase Reference)
• NIST Chemistry Reference: 3-Fluorobenzyl chloride(456-42-8)
• EPA Substance Registry System: 3-Fluorobenzyl chloride(456-42-8)

Safety Data

• Hazard Codes: C
• Statements: 34-37
• Safety Statements: 26-36/37/39-45
• RIDADR: UN 2920 8/PG 2
• WGK Germany: 3
• TSCA: Yes
• HazardClass: 3
• PackingGroup: III
• Hazardous Substances Data: 456-42-8(Hazardous Substances Data)

Usage

Chemical Properties

Colorless to light yellow liqui

InChI:InChI=1/C7H6ClF/c8-5-6-2-1-3-7(9)4-6/h1-4H,5H2

Synthetic route

m-Fluorotoluene (352-70-5) → m-fluorobenzyl chloride (456-42-8)

Conditions	Yield
With methanol; tetrachloromethane; iron(II) chloride tetrahydrate; formamide at 180℃; for 6h; Reagent/catalyst; Inert atmosphere; Sealed tube; Autoclave; chemoselective reaction;	35%
at 147℃; Irradiation.Einleiten von Chlor;
at 147℃; Einleiten von Chlor;

m-Fluorotoluene (352-70-5) → 1-dichloromethyl-3-fluoro-benzene (402-64-2) + m-fluorobenzyl chloride (456-42-8)

Conditions	Yield
Chlorierung;

3-fluoro-benzenemethanol (456-47-3) → m-fluorobenzyl chloride (456-42-8)

Conditions	Yield
With pyridine; thionyl chloride

1-fluoro-3-(iodomethyl)benzene (28490-56-4) → m-fluorobenzyl chloride (456-42-8)

Conditions	Yield
With pyridine; tributyltin chloride at 50℃; Thermodynamic data; Equilibrium constant; Δ G;	28 % Spectr.

m-fluorobenzyl ion (65108-06-7) → m-fluorobenzyl chloride (456-42-8)

Conditions	Yield
With tertiary butyl chloride In gaseous matrix at 600℃; chloride affinity;

1-(Bromomethyl)-3-fluorobenzene (456-41-7) → m-fluorobenzyl chloride (456-42-8)

Conditions	Yield
With pyridine; tributyltin chloride at 50℃; Thermodynamic data; Equilibrium constant; Δ G;	65 % Spectr.

1-bromomethyl-4-nitro-benzene (100-11-8) → m-fluorobenzyl chloride (456-42-8)

Conditions	Yield
With pyridine; tributyltin chloride at 50℃; Thermodynamic data; Equilibrium constant; Δ G;	65 % Spectr.

1-(1-chloro-2,2,2-trifluoroethyl)-4-chlorobenzene (394-54-7) + m-fluorobenzyl ion (65108-06-7) → C8H5ClF3(1+) (128408-33-3) + m-fluorobenzyl chloride (456-42-8)

Conditions	Yield
at 69.85℃; Thermodynamic data; chloride-transfer;

1-(1-Chloro-2,2,2-trifluoro-ethyl)-3-methyl-benzene (191402-55-8) + m-fluorobenzyl ion (65108-06-7) → C9H8F3(1+) (128408-28-6) + m-fluorobenzyl chloride (456-42-8)

Conditions	Yield
at 69.85℃; Thermodynamic data; chloride-transfer;

1-(1-Chloro-2,2,2-trifluoro-ethyl)-4-fluoro-benzene (81577-13-1) + m-fluorobenzyl ion (65108-06-7) → C8H5F4(1+) (128408-32-2) + m-fluorobenzyl chloride (456-42-8)

Conditions	Yield
at 69.85℃; Thermodynamic data; chloride-transfer;

2-Chloro-4-(1-chloro-2,2,2-trifluoro-ethyl)-1-methyl-benzene + m-fluorobenzyl ion (65108-06-7) → C9H7ClF3(1+) (128408-27-5) + m-fluorobenzyl chloride (456-42-8)

Conditions	Yield
at 69.85℃; Thermodynamic data; chloride-transfer;

3-fluoro-toluene-vapour → m-fluorobenzyl chloride (456-42-8)

Conditions	Yield
With chlorine

(Z)-6-methoxy-2-(pyridin-4-ylmethylene)benzofuran-3(2H)-one (1178094-73-9) + m-fluorobenzyl chloride (456-42-8) → (Z)-1-(3-fluorobenzyl)-4-((6-methoxy-3-oxobenzofuran-2(3H)-ylidene)methyl)pyridinium chloride (1250364-30-7)

Conditions	Yield
In acetonitrile Reflux;	100%

(Z)-6-ethoxy-2-(pyridin-4-ylmethylene)benzofuran-3(2H)-one (1250364-18-1) + m-fluorobenzyl chloride (456-42-8) → (Z)-1-(3-fluorobenzyl)-4-((6-ethoxy-3-oxobenzofuran-2(3H)-ylidene)methyl)pyridinium chloride (1250364-43-2)

Conditions	Yield
In acetonitrile Reflux;	100%

(Z)-6-propoxy-2-(pyridin-4-ylmethylene)benzofuran-3(2H)-one (1250364-19-2) + m-fluorobenzyl chloride (456-42-8) → (Z)-1-(3-fluorobenzyl)-4-((6-propoxy-3-oxobenzofuran-2(3H)-ylidene)methyl)pyridinium chloride (1250364-55-6)

Conditions	Yield
In acetonitrile Reflux;	100%

mercaptoacetic acid (68-11-1) + m-fluorobenzyl chloride (456-42-8) → 2-(3-fluorobenzylthio)acetic acid

Conditions	Yield
With sodium hydroxide In methanol at 20℃; for 1h;	98.1%

carbon dioxide (124-38-9) + m-fluorobenzyl chloride (456-42-8) → (3-fluorophenyl)acetic acid (331-25-9)

Conditions	Yield
With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; manganese; palladium diacetate; magnesium chloride In N,N-dimethyl-formamide under 760.051 Torr; for 12h; Inert atmosphere; Schlenk technique;	96%

m-fluorobenzyl chloride (456-42-8) + C19H22Cl3NO3 (214326-07-5) → C26H27Cl3FNO3 (214325-98-1)

Conditions	Yield
With potassium carbonate In ethanol Heating;	95%

4-hydroxy-benzaldehyde (123-08-0) + m-fluorobenzyl chloride (456-42-8) → 4-(3-fluoro-benzyloxy)-benzaldehyde (66742-57-2)

Conditions	Yield
With potassium carbonate; sodium iodide In ethanol for 5.41667h; Product distribution / selectivity; Heating / reflux;	95%
With sodium hydroxide In ethanol for 6.75h; Product distribution / selectivity; Heating / reflux;	95%
With potassium carbonate; sodium iodide In ethanol for 5.41667h; Product distribution / selectivity; Heating / reflux;	95%

m-fluorobenzyl chloride (456-42-8) + (E)-3-(pyridin-4-ylmethylene)indolin-2-one (128564-78-3) → (E)-1-(3-fluorobenzyl)-4-((2-oxoindolin-3-ylidene)methyl)pyridinium chloride (1621102-53-1)

Conditions	Yield
In acetonitrile at 60 - 70℃;	95%

2-amino-benzenethiol (137-07-5) + m-fluorobenzyl chloride (456-42-8) → 2-(3-fluorophenyl)benzo[d]thiazole (1629-07-8)

Conditions	Yield
With pyridine; sulfur at 130℃; for 20h; Inert atmosphere;	95%

2-Chloronitrobenzene (88-73-3) + m-fluorobenzyl chloride (456-42-8) → 2-(3-fluorophenyl)benzo[d]thiazole (1629-07-8)

Conditions	Yield
With N-methylcyclohexylamine; sulfur at 110℃; for 24h; Sealed tube; Inert atmosphere;	95%

demethyltetrandrine (436-77-1, 10172-02-8, 33889-68-8, 38769-07-2, 53834-87-0, 119478-08-9) + m-fluorobenzyl chloride (456-42-8) → C44H45FN2O6*2HCl

Conditions	Yield
Stage #1: demethyltetrandrine; m-fluorobenzyl chloride With tetrabutylammomium bromide In water at 120℃; for 1h; Sonication; Stage #2: With hydrogenchloride In water Reagent/catalyst; Solvent; Temperature; Molecular sieve;	94.77%

2-amino-4-methoxy-N-(8-azabicyclo<3,2,1>oct-3 β-yl)-5-pyrimidine carboxamide (76352-25-5) + m-fluorobenzyl chloride (456-42-8) → 2-Amino-4-methoxy-pyrimidine-5-carboxylic acid [(1R,3S,5S)-8-(3-fluoro-benzyl)-8-aza-bicyclo[3.2.1]oct-3-yl]-amide (84922-97-4)

Conditions	Yield
With potassium carbonate In acetone for 36h; Heating;	94%

m-fluorobenzyl chloride (456-42-8) + 1-(4-fluoro-phenyl)-2-(tetrahydro-pyrimidin-2-ylidene)-ethanone (251940-05-3) → 3-(3'-fluorophenyl)-1-(4'-fluoro-phenyl)-2-(tetrahydropyrimidin-2'-ylidene)-propan-1-one

Conditions	Yield
In toluene at 65℃; for 2h;	94%

6,7-dimethoxyisoquinoline-1(2H)-one (16101-63-6) + m-fluorobenzyl chloride (456-42-8) → 2-(3-fluorobenzyl)-6,7-dimethoxyisoquinolin-1(2H)-one

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 20℃; for 0.5h; Inert atmosphere;	93.1%

1-phenyl-2-(tetrahydropyrimidin-2(1H)-ylidene)ethan-1-one (82100-30-9) + m-fluorobenzyl chloride (456-42-8) → 3-(3'-fluoro-phenyl)-1-phenyl-2-(tetrahydropyrimidin-2'-ylidene)-propan-1-one

Conditions	Yield
In toluene at 60℃; for 2h;	93%

N,2,5-trimethoxy-N-methylbenzamide (1146443-78-8) + m-fluorobenzyl chloride (456-42-8) → 1-(2,5-dimethoxyphenyl)-2-(3-fluorophenyl)ethanone (1097077-65-0)

Conditions	Yield
Stage #1: m-fluorobenzyl chloride With magnesium In diethyl ether at 0 - 20℃; for 4h; Stage #2: N,2,5-trimethoxy-N-methylbenzamide In tetrahydrofuran; diethyl ether at 0℃; for 1h;	93%
Stage #1: m-fluorobenzyl chloride With iodine; magnesium In tetrahydrofuran at 0℃; Stage #2: N,2,5-trimethoxy-N-methylbenzamide In tetrahydrofuran at 0℃; for 1h;

2‐amino‐4‐(pyridin‐4‐yl)‐5‐oxo‐4H,5H‐pyrano[3,2‐c]chromene‐3‐carbonitrile + m-fluorobenzyl chloride (456-42-8) → 4-(2-amino-3-cyano-5-oxo-4,5-dihydropyrano[3,2-c]chromen-4-yl)-1-(3-fluorobenzyl)pyridinium chloride

Conditions	Yield
With potassium iodide In acetonitrile Reflux;	93%

8-chloro-[1,2,4]triazolo[4,3-a]pyridine-3(2H)-thione (22841-91-4) + m-fluorobenzyl chloride (456-42-8) → 8-chloro-3-((3-fluorobenzyl)thio)-[1,2,4]triazolo[4,3-a]pyridine

Conditions	Yield
With sodium hydroxide In N,N-dimethyl-formamide at 90℃; for 0.25h; Microwave irradiation;	93%
With sodium hydroxide In N,N-dimethyl-formamide at 90℃; for 0.25h; Microwave irradiation;	81%

2-iodophenylamine (615-43-0) + m-fluorobenzyl chloride (456-42-8) → 2-(3-fluorophenyl)benzo[d]thiazole (1629-07-8)

Conditions	Yield
With copper(II) acetate monohydrate; sodium carbonate; sulfur In dimethyl sulfoxide at 130℃; for 24h; Schlenk technique; Inert atmosphere;	93%

2-methylamino-5-mercapto-1,3,4-thiadiazole (27386-01-2) + m-fluorobenzyl chloride (456-42-8) → 2-(3-fluorobenzylthio)-5-methylamino-1,3,4-thiadiazole (97773-03-0)

Conditions	Yield
With potassium hydroxide In methanol for 0.5h; Ambient temperature;	92%

oxalic acid diethyl ester (95-92-1) + m-fluorobenzyl chloride (456-42-8) → 3-(3-fluorophenyl)-2-oxopropionic acid ethyl ester

Conditions	Yield
Stage #1: m-fluorobenzyl chloride With magnesium In diethyl ether for 0.166667h; Heating; Stage #2: oxalic acid diethyl ester In diethyl ether at 20℃; for 2h; Grignard reaction;	92%

CH3C6H3OCHCNC(CONH) (918156-44-2) + m-fluorobenzyl chloride (456-42-8) → CH3C6H3OCHCNC(CON)CH2C6H4F

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 20℃; for 12h;	92%

N-methylacetohydroxamic acid (13115-24-7) + m-fluorobenzyl chloride (456-42-8) → N-((3-fluorobenzyl)oxy)-N-methylacetamide (1352918-96-7)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 12h; Inert atmosphere;	92%

allylbenzene (300-57-2) + m-fluorobenzyl chloride (456-42-8) → 1-(2-benzylallyl)-3-fluorobenzene (1419174-93-8)

Conditions	Yield
With trimethylsilyl trifluoromethanesulfonate; trans-bis(dicyclohexylphenylphosphine)(2-methylphenyl)nickel(II) chloride; triethylamine In dichloromethane at 20℃; for 4h; Heck Reaction; regioselective reaction;	92%

5-chloro-2-benzoxazolinone (95-25-0) + m-fluorobenzyl chloride (456-42-8) → 5-chloro-3-(3-fluorobenzyl)benzo[d]oxazol-2(3H)-one

Conditions	Yield
Stage #1: 5-chloro-2-benzoxazolinone With potassium carbonate In N,N-dimethyl-formamide at 90℃; for 1h; Stage #2: m-fluorobenzyl chloride In N,N-dimethyl-formamide at 60℃; for 7h;	92%

aniline (62-53-3) + m-fluorobenzyl chloride (456-42-8) → N-(3-fluorobenzyl)aniline (83444-26-2)

Conditions	Yield
With sodium carbonate at 110℃; for 1h;	90%

2-fluorophenol (367-12-4) + m-fluorobenzyl chloride (456-42-8) → C13H10F2O

Conditions	Yield
With sodium In ethanol for 2h; Heating;	90%

(3R,6S)-hexahydrofuro[3,2-b]furan-3,6-diol (1214839-99-2) + m-fluorobenzyl chloride (456-42-8) → (3R,6S)-3,6-Bis-(3-fluoro-benzyloxy)-hexahydro-furo[3,2-b]furan

Conditions	Yield
With potassium hydroxide; tetrabutylammomium bromide In xylene at 125℃; for 0.0833333h; Alkylation; microwave irradiation;	90%

1-(4-chlorophenyl)-2-(tetrahydropyrimidin-2(1H)-ylidene)ethan-1-one (107165-83-3) + m-fluorobenzyl chloride (456-42-8) → 1-(4'-chloro-phenyl)-3-(3'-fluoro-phenyl)-2-(tetrahydropyrimidin-2'-ylidene)-propan-1-one

Conditions	Yield
In toluene at 65℃; for 3h;	90%

m-fluorobenzyl chloride (456-42-8) + 5-nitroindazole (5401-94-5) → 1-(3-fluorobenzyl)-5-nitro-1H-carbazole (529508-58-5) + 1-(3-fluorobenzyl)-1H-indazol-5-ylamine (202197-31-7)

Conditions	Yield
With Ki; potassium carbonate In water; N,N-dimethyl-formamide	A 33% B 90%

Upstream product

• 456-41-7 1-(Bromomethyl)-3-fluorobenzene 
• 394-54-7 1-chloro-1-(4-chlorophenyl)-2,2,2-trifluoroethane 
• 65108-06-7 m-fluorobenzyl ion 
• 81577-13-1 1-(1-Chloro-2,2,2-trifluoro-ethyl)-4-fluoro-benzene 
• 191402-55-8 1-(1-Chloro-2,2,2-trifluoro-ethyl)-3-methyl-benzene 
• 100-11-8 1-bromomethyl-4-nitro-benzene 
• 28490-56-4 1-fluoro-3-(iodomethyl)benzene 
• 456-47-3 3-fluoro-benzenemethanol 
• 352-70-5 m-Fluorotoluene 

Downstream Products

• 405-11-8 (2-bromo-4-methyl-phenyl)-(3-fluoro-benzyl)-ether 
• 458-60-6 (4-bromo-2-methyl-phenyl)-(3-fluoro-benzyl)-ether 
• 332-02-5 (4-chloro-phenyl)-(3-fluoro-benzyl)-ether 
• 1496-00-0 1-benzyl-3-fluorobenzene 
• 405-85-6 4-(3-fluorobenzyloxy)benzoic acid 
• 402-64-2 1-dichloromethyl-3-fluoro-benzene 
• 456-47-3 3-fluoro-benzenemethanol 
• 456-48-4 3-Fluorobenzaldehyde 
• 27856-34-4 m-Fluorbenzyl-dimethylsilan 
• 772-48-5 <3-Fluor-benzyl>-trimethyl-silan 
• 65354-71-4 2-(m-Fluorophenyl)isopropylidenecyclopropane 
• 65354-65-6 2-(m-Fluorophenyl)-3,3-dimethylmethylenecyclopropane 
• 24788-08-7 1-(2,2-Dimethyl-propyl)-3-fluoro-benzene 
• 501-00-8 3-fluorophenylacetonitrile 

Relevant articles and documents

Synthesis of mono- and difluorobenzyl chlorides by chlorination of mono- and difluorotoluenes with CCl4 and t-BuOCl induced by iron-containing catalysts

Mono- and difluorobenzyl chlorides were synthesized by chlorination of mono- and difluorotoluenes with CCl4?MeOH or t-BuOCl in the presence of iron-containing catalysts.

STEROID RECEPTOR MODULATOR COMPOUNDS AND METHODS

Non-steroidal compounds which are high affinity, high selectivity modulators for steroid receptors are disclosed. Also disclosed are pharmaceutical compositions incorporating such compounds, methods for employing the disclosed compounds and compositions for treating patients requiring steroid receptor agonist or antagonist therapy, intermediates useful in the preparation of the compounds and processes for the preparation of the steroid receptor modulator compounds.

STEROID RECEPTOR MODULATOR COMPOUNDS AND METHODS

Non-steroidal compounds which are high affinity, high selectivity modulators for steroid receptors are disclosed. Also disclosed are pharmaceutical compositions incorporating such compounds, methods for employing the disclosed compounds and compositions for treating patients requiring steroid receptor agonist or antagonist therapy, intermediates useful in the preparation of the compounds and processes for the preparation of the steroid receptor modulator compounds.