74457-86-6

Basic information

• Product Name: 2-Fluoro-4-methoxyacetophenone
• Synonyms: 2'-Fluoro-4'-Methoxyacetoph...;Ethanone, 1-(2-fluoro-4-Methoxyphenyl)-;2'-Fluoro-4'-methoxylacetophenone;2'-FLUORO-4'-METHOXYACETOPHENONE;2-FLUORO-4-METHOXYACETOPHENONE;1-(2-FLUORO-4-METHOXYPHENYL)ETHANONE;4-ACETYL-3-FLUOROANISOLE;2-FLUORO-4-METHOXYACETOPHENONE 99% (HP&
• CAS NO: 74457-86-6
• Molecular Formula: C₉H₉FO₂
• Molecular Weight: 168.16
• Product Categories: Fluorine series;Aromatic Acetophenones & Derivatives (substituted);Adehydes, Acetals & Ketones;Anisoles, Alkyloxy Compounds & Phenylacetates;Fluorine Compounds;C9;Carbonyl Compounds;Ketones
• Mol File: 74457-86-6.mol
• Article Data: 7

Chemical Properties

• Melting Point: 52-54 °C(lit.)
• Boiling Point: 80-85 °C (0.1 mmHg)
• Flash Point: >230 °F
• Appearance: Clear colorless/Viscous Solution
• Density: 1.1410 (estimate)
• Storage Temp.: Sealed in dry,Room Temperature
• Water Solubility: Insoluble
• BRN: 3539992
• CAS DataBase Reference: 2-Fluoro-4-methoxyacetophenone(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Fluoro-4-methoxyacetophenone(74457-86-6)
• EPA Substance Registry System: 2-Fluoro-4-methoxyacetophenone(74457-86-6)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36-37/39
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 74457-86-6(Hazardous Substances Data)

Usage

Chemical Properties

white to light yellow crystal powder

Uses

2′-Fluoro-4′-methoxyacetophenone may be used in chemical synthesis.

Preparation

Obtained by reaction of acetic anhydride with 3-fluoroanisole in the presence of aluminium chloride in carbon disulfide at r.t., then at 30–35° until no more hydrochloric acid is evolved.

Synthetic route

1-(4-methoxyphenyl)ethanone (100-06-1) → 1-(2-fluoro-4-methoxyphenyl)-1-ethanone (74457-86-6)

Conditions	Yield
With palladium diacetate; silver nitrate; N-fluorobis(benzenesulfon)imide; methyl carbamate In dichloromethane at 95℃; for 24h; Sealed tube;	78%
Multi-step reaction with 3 steps 1: sodium acetate / ethanol; water / 2 h / Reflux 2: tris(dibenzylideneacetone)dipalladium(0) chloroform complex; N-fluorobis(benzenesulfon)imide; potassium nitrate / nitromethane / 24 h / 25 °C 3: hydrogenchloride; water / diethyl ether / 30 h / 20 °C View Scheme

1-fluoro-3-methoxybenzene (456-49-5) + acetic anhydride (108-24-7) → 1-(4-fluoro-2-methoxy-phenyl)-ethanone (51788-80-8) + 1-(2-fluoro-4-methoxyphenyl)-1-ethanone (74457-86-6)

Conditions	Yield
With lithium perchlorate at 100℃; for 1h;	A 30% B 70%

1-fluoro-3-methoxybenzene (456-49-5) + acetic anhydride (108-24-7) → 1-(2-fluoro-4-methoxyphenyl)-1-ethanone (74457-86-6)

Conditions	Yield
With aluminium trichloride In carbon disulfide at 20 - 35℃;	60.7%
With aluminium trichloride In 1,2-dichloro-ethane for 2h; Ambient temperature;

1-fluoro-3-methoxybenzene (456-49-5) → 1-(2-fluoro-4-methoxyphenyl)-1-ethanone (74457-86-6)

C10H12FNO2 (1313430-15-7) → 1-(2-fluoro-4-methoxyphenyl)-1-ethanone (74457-86-6)

Conditions	Yield
With hydrogenchloride; water In diethyl ether at 20℃; for 30h;	26.5 mg

1-(2-fluoro-4-methoxyphenyl)-1-ethanone (74457-86-6) + methylmagnesium chloride (676-58-4) → 2-(2-fluoro-4-methoxyphenyl)-2-isopropanol (96826-25-4)

Conditions	Yield
Stage #1: 1-(2-fluoro-4-methoxyphenyl)-1-ethanone; methylmagnesium chloride In tetrahydrofuran; dichloromethane at 0℃; Inert atmosphere; Stage #2: With hydrogenchloride; methanol; water In tetrahydrofuran; dichloromethane at 20℃; Product distribution / selectivity;	99%
Stage #1: 1-(2-fluoro-4-methoxyphenyl)-1-ethanone; methylmagnesium chloride In tetrahydrofuran at 20 - 35℃; for 0.666667h; Inert atmosphere; Stage #2: With water; acetic acid In tetrahydrofuran at 5 - 25℃;	98%
In tetrahydrofuran at -15 - 0℃; for 1h;	95%

1-(2-fluoro-4-methoxyphenyl)-1-ethanone (74457-86-6) → 2-fluoro-4-methoxy-phenol (167683-93-4)

Conditions	Yield
Stage #1: 1-(2-fluoro-4-methoxyphenyl)-1-ethanone With magnesium sulfate; 3-chloro-benzenecarboperoxoic acid In chloroform at 20℃; for 120h; Stage #2: With ammonium hydroxide In methanol; acetonitrile at 20℃; for 3h; Further stages.;	98%
Multi-step reaction with 2 steps 1: mCPBA, MgSO4 / CHCl3 / 12 h / Ambient temperature 2: 94 percent / aq. NH3 / methanol / 1 h / Ambient temperature View Scheme

NH3 (aq) + 1-(2-fluoro-4-methoxyphenyl)-1-ethanone (74457-86-6) → 2-fluoro-4-methoxy-phenol (167683-93-4)

Conditions	Yield
In methanol	94%

1-(2-fluoro-4-methoxyphenyl)-1-ethanone (74457-86-6) → (E)-1-(2-fluoro-4-methoxyphenyl)ethanone oxime (1434602-18-2)

Conditions	Yield
With hydroxylamine hydrochloride; sodium carbonate In ethanol; water pH=5; Reflux;	93%

1-(2-fluoro-4-methoxyphenyl)-1-ethanone (74457-86-6) → 1-(2,6-difluoro-4-methoxyphenyl)ethan-1-one

Conditions	Yield
With palladium diacetate; silver nitrate; N-fluorobis(benzenesulfon)imide; methyl carbamate In dichloromethane at 95℃; for 24h; Sealed tube;	93%

1-(2-fluoro-4-methoxyphenyl)-1-ethanone (74457-86-6) → 1-(2-fluoro-4-methoxyphenyl)ethan-1-ol (74457-87-7)

Conditions	Yield
With lithium aluminium tetrahydride In diethyl ether 1.) RT, 3 h, 2.) reflux, 1 h;	92%

1-(2-fluoro-4-methoxyphenyl)-1-ethanone (74457-86-6) + oxalic acid diethyl ester (95-92-1) → ethyl 4-(2-fluoro-4-methoxyphenyl)-2,4-dioxobutanoate

Conditions	Yield
Stage #1: 1-(2-fluoro-4-methoxyphenyl)-1-ethanone; oxalic acid diethyl ester With sodium ethanolate In ethanol at 20℃; Inert atmosphere; Stage #2: With hydrogenchloride In water	91.2%

1-(2-fluoro-4-methoxyphenyl)-1-ethanone (74457-86-6) + oxalic acid diethyl ester (95-92-1) → ethyl (Z)-4-(2-fluoro-4-methoxyphenyl)-2-hydroxy-4-oxobut-2-enoate

Conditions	Yield
With potassium tert-butylate In tetrahydrofuran at 20℃; Claisen Condensation;	91%

1-(2-fluoro-4-methoxyphenyl)-1-ethanone (74457-86-6) + 4-methoxy-benzaldehyde (123-11-5) → E-1-(2-fluoro-4-methoxyphenyl)-3-(4-methoxyphenyl)-2-propen-1-one

Conditions	Yield
With sodium hydroxide In ethanol; water for 12h; Ambient temperature;	90%

1-(2-fluoro-4-methoxyphenyl)-1-ethanone (74457-86-6) → 6-methoxy-3-methyl-1H-indazole (7746-29-4)

Conditions	Yield
Stage #1: 1-(2-fluoro-4-methoxyphenyl)-1-ethanone With hydrazine hydrate In ethanol for 6h; Reflux; Stage #2: With ethylene glycol at 150℃; for 96h;	90%
With hydrazine hydrate In 1-methyl-pyrrolidin-2-one at 120℃; for 24h; Inert atmosphere;	78%
With hydrazine hydrate In ethanol; ethylene glycol	59%

1-(2-fluoro-4-methoxyphenyl)-1-ethanone (74457-86-6) + Methyltriphenylphosphonium bromide (1779-49-3) → 2-fluoro-4-methoxy-1-(prop-1-en-2-yl)benzene (875446-55-2)

Conditions	Yield
Stage #1: Methyltriphenylphosphonium bromide With potassium tert-butylate In toluene at 20℃; for 0.5h; Inert atmosphere; Stage #2: 1-(2-fluoro-4-methoxyphenyl)-1-ethanone In toluene at 20℃; for 4h; Inert atmosphere;	88%
Stage #1: Methyltriphenylphosphonium bromide With sodium hexamethyldisilazane In tetrahydrofuran for 0.5h; Cooling with ice; Stage #2: 1-(2-fluoro-4-methoxyphenyl)-1-ethanone In tetrahydrofuran at -78 - 20℃;	63%
Stage #1: Methyltriphenylphosphonium bromide With sodium hexamethyldisilazane In tetrahydrofuran at 0℃; for 0.5h; Stage #2: 1-(2-fluoro-4-methoxyphenyl)-1-ethanone In tetrahydrofuran at -78 - 20℃; for 2.5h; Stage #3: With acetic acid In tetrahydrofuran for 0.5h;
Stage #1: Methyltriphenylphosphonium bromide With potassium tert-butylate In toluene at 40 - 50℃; for 2h; Inert atmosphere; Stage #2: 1-(2-fluoro-4-methoxyphenyl)-1-ethanone In toluene at 55 - 65℃; for 2h; Wittig Olefination; Inert atmosphere;	233 g

1-(2-fluoro-4-methoxyphenyl)-1-ethanone (74457-86-6) + 2,3,4-trimethoxybenzaldehyde (2103-57-3) → 1-(2-fluoro-4-methoxyphenyl)-3-(2,3,4-trimethoxyphenyl)prop-2-ene-1-one

Conditions	Yield
With sodium hydroxide In ethanol at 20℃; for 3h; Claisen-Schmidt Condensation;	87.18%

1-(2-fluoro-4-methoxyphenyl)-1-ethanone (74457-86-6) + 2,4-Dimethoxybenzaldehyde (613-45-6) → 1-(2-fluoro-4-methoxyphenyl)-3-(2,4-dimethoxyphenyl)prop-2-ene-1-one

Conditions	Yield
With sodium hydroxide In ethanol at 20℃; for 3h; Claisen-Schmidt Condensation;	85.18%

1-(2-fluoro-4-methoxyphenyl)-1-ethanone (74457-86-6) + C9H6F3NO4 → (E)-1-(2-fluoro-4-methoxyphenyl)-3-(2-nitro-5-(2,2,2-trifluoroethoxy)phenyl)prop-2-en-1-one

Conditions	Yield
With sodium hydroxide In ethanol; water; acetonitrile at 20℃; for 1h; Aldol Condensation;	84%

4-piperidinemethanol (6457-49-4) + 1-(2-fluoro-4-methoxyphenyl)-1-ethanone (74457-86-6) → 1-(2-(4-(hydroxymethyl)piperidin-1-yl)-4-methoxyphenyl)-ethanone

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide at 130℃; Reagent/catalyst; Solvent; Temperature;	84%

1-(2-fluoro-4-methoxyphenyl)-1-ethanone (74457-86-6) → 2-(2-fluoro-4-methoxyphenyl)-2-methylethanenitrile

Conditions	Yield
With potassium tert-butylate In 1,2-dimethoxyethane; (2S)-N-methyl-1-phenylpropan-2-amine hydrate	83%
With potassium tert-butylate In 1,2-dimethoxyethane; (2S)-N-methyl-1-phenylpropan-2-amine hydrate	83%

1-(2-fluoro-4-methoxyphenyl)-1-ethanone (74457-86-6) + 3,4,5-trimethoxy-benzaldehyde (86-81-7) → 1-(2-fluoro-4-methoxyphenyl)-3-(3,4,5-trimethoxyphenyl)prop-2-ene-1-one

Conditions	Yield
With sodium hydroxide In ethanol at 20℃; for 3h; Claisen-Schmidt Condensation;	82.3%

2,4,6-trimethoxybenzaldehyde (830-79-5) + 1-(2-fluoro-4-methoxyphenyl)-1-ethanone (74457-86-6) → 1-(2-fluoro-4-methoxyphenyl)-3-(2,4,6-trimethoxyphenyl)-prop-2-ene-1-one

Conditions	Yield
With sodium hydroxide In ethanol at 20℃; for 3h; Claisen-Schmidt Condensation;	82.1%

1-(2-fluoro-4-methoxyphenyl)-1-ethanone (74457-86-6) → 1-(2-fluoro-4-methoxy-3-nitro-phenyl)-ethanone (1414877-13-6) + 1-(2-fluoro-4-methoxy-5-nitro-phenyl)-ethanone (1414877-12-5)

Conditions	Yield
With sulfuric acid; nitric acid at -20 - -15℃; for 0.666667h;	A 2% B 82%

asaraldehyde (4460-86-0) + 1-(2-fluoro-4-methoxyphenyl)-1-ethanone (74457-86-6) → 1-(2-fluoro-4-methoxyphenyl)-3-(2,4,5-trimethoxyphenyl)prop-2-ene-1-one

Conditions	Yield
With sodium hydroxide In ethanol at 20℃; for 3h; Claisen-Schmidt Condensation;	80.2%

1-(2-fluoro-4-methoxyphenyl)-1-ethanone (74457-86-6) + 2,6-dichloro-4-methoxy-benzaldehyde (82772-93-8) → E-1-(2-fluoro-4-methoxyphenyl)-3-(2,6-dichloro-4-methoxyphenyl)-2-propen-1-one

Conditions	Yield
With sodium hydroxide In ethanol for 4h; Ambient temperature;	80%

1-(2-fluoro-4-methoxyphenyl)-1-ethanone (74457-86-6) + 2-(trifluoromethyl)benzenamine (88-17-5) → N-[2-(dimethylamino)ethyl]-2-(2-fluoro-4-methoxyphenyl)quinolin-4-amine

Conditions	Yield
1-(2-fluoro-4-methoxyphenyl)-1-ethanone; 2-(trifluoromethyl)benzenamine With toluene-4-sulfonic acid In xylene Heating; Further stages.;	80%

methylmagnesium bromide (75-16-1) + 1-(2-fluoro-4-methoxyphenyl)-1-ethanone (74457-86-6) → 2-(2-fluoro-4-methoxyphenyl)-2-isopropanol (96826-25-4)

Conditions	Yield
In tetrahydrofuran at 0 - 20℃; Inert atmosphere;	80%
Stage #1: methylmagnesium bromide; 1-(2-fluoro-4-methoxyphenyl)-1-ethanone In tetrahydrofuran at 0 - 20℃; for 4h; Stage #2: With water; ammonium chloride In tetrahydrofuran
In tetrahydrofuran at 0 - 20℃; for 4h;
In tetrahydrofuran at 0 - 20℃; for 4h;
In tetrahydrofuran at 0℃; for 4h;

1-(2-fluoro-4-methoxyphenyl)-1-ethanone (74457-86-6) + phenylmethanethiol (100-53-8) → 1-(2-(benzylthio)-4-methoxyphenyl)ethan-1-one

Conditions	Yield
Stage #1: phenylmethanethiol With potassium tert-butylate In tetrahydrofuran for 1h; Inert atmosphere; Stage #2: 1-(2-fluoro-4-methoxyphenyl)-1-ethanone In tetrahydrofuran for 3h; Reflux;	80%

3,5-dimethoxybenzaldehdye (7311-34-4) + 1-(2-fluoro-4-methoxyphenyl)-1-ethanone (74457-86-6) → 1-(2-fluoro-4-methoxyphenyl)-3-(3,5-dimethoxyphenyl)prop-2-ene-1-one

Conditions	Yield
With sodium hydroxide In ethanol at 20℃; for 3h; Claisen-Schmidt Condensation;	79.4%

2,5-bis(trifluoromethyl)aniline (328-93-8) + 1-(2-fluoro-4-methoxyphenyl)-1-ethanone (74457-86-6) → N-[2-(dimethylamino)ethyl]-7-trifluoromethyl-2-[(2-fluoro-4-methoxy)phenyl]quinolin-4-amine

Conditions	Yield
2,5-bis(trifluoromethyl)aniline; 1-(2-fluoro-4-methoxyphenyl)-1-ethanone With toluene-4-sulfonic acid In xylene Heating; Further stages.;	75%

isochromane (493-05-0) + 1-(2-fluoro-4-methoxyphenyl)-1-ethanone (74457-86-6) → 1-(2-fluoro-4-methoxyphenyl)-2-(isochroman-1-yl)ethanone

Conditions	Yield
With carbon tetrabromide In neat (no solvent) at 100℃; for 48h;	75%

6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (1745-07-9) + 1-(2-fluoro-4-methoxyphenyl)-1-ethanone (74457-86-6) → 1-(2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-4-methoxyphenyl)ethanone

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 20.5h; Inert atmosphere;	72%

Upstream product

• 456-49-5 1-fluoro-3-methoxybenzene 
• 108-24-7 acetic anhydride 
• 1313430-15-7 C₁₀H₁₂FNO₂ 
• 100-06-1 1-(4-methoxyphenyl)ethanone 

Downstream Products

• 875446-55-2 2-fluoro-4-methoxy-1-(prop-1-en-2-yl)benzene 
• 1383814-83-2 4-fluoro-2-methoxy-5-(2-propenyl)phenylboronic acid 
• 1383814-82-1 1-bromo-4-fluoro-2-methoxy-5-(1-methylvinyl)benzene 
• 958029-46-4 2-(5-bromo-2-fluoro-4-methoxyphenyl)propan-2-ol 
• 1351403-10-5 2-fluoro-4-methoxy-1-ethylbenzene 
• 875551-28-3 2'-(chloromethyl)-4-fluoro-5-isopropyl-2-methoxy-4'-(trifluoromethyl)biphenyl 
• 944317-92-4 1-bromo-4-fluoro-2-methoxy-5-(propan-2-yl)-benzene 
• 875446-37-0 anacetrapib 
• 1383676-66-1 1-bromo-5-ethyl-4-fluoro-2-methoxybenzene 
• 1383676-67-2 5-ethyl-4-fluoro-2-methoxyphenylboronic acid 
• 1312671-75-2 5-[3,5-bis(trifluoromethyl)phenyl]-3-{[4'-fluoro-2'-methoxy-5'-(propan-2-yl)-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4,4-dimethyl-1,3-oxazolidin-2-one 
• 875548-98-4 2'-(bromomethyl)-4-fluoro-2-methoxy-5-(propan-2-yl)-4'-(trifluoromethyl)biphenyl 
• 1262414-96-9 2-(2-fluoro-4-methoxyphenyl)isopropane 
• 875446-57-4 1-fluoro-4-iodo-2-isopropenyl-5-methoxybenzene 

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