6836-21-1

Basic information

• Product Name: 7-Methoxy-1-naphthaleneacetic acid ethyl ester
• Synonyms: Ethyl 2-(7-Methoxynaphthalen-1-yl)acetate;Ethyl (7-Methoxynaphthalen-1-yl)acetate;Ethyl 2-(7-methoxynaphthalen-1-yl);7-Methoxy-1-phthaleneacetic acid ethyl ester;7-Methoxy-1-naphthaleneacetic acid ethyl ester;Ethyl 7-Methoxynaphthalene-1-acetate
• CAS NO: 6836-21-1
• Molecular Formula: C₁₅H₁₆O₃
• Molecular Weight: 244.29
• EINECS: 1312995-182-4
• Product Categories: Agomelatine Intermediate
• Mol File: 6836-21-1.mol
• Article Data: 9

Chemical Properties

• Boiling Point: 370.4ºC at 760 mmHg
• Flash Point: 155.1ºC
• Appearance: /
• Density: 1.126
• Vapor Pressure: 1.11E-05mmHg at 25°C
• Refractive Index: 1.572
• Storage Temp.: Sealed in dry,Room Temperature
• CAS DataBase Reference: 7-Methoxy-1-naphthaleneacetic acid ethyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: 7-Methoxy-1-naphthaleneacetic acid ethyl ester(6836-21-1)
• EPA Substance Registry System: 7-Methoxy-1-naphthaleneacetic acid ethyl ester(6836-21-1)

Safety Data

• Hazardous Substances Data: 6836-21-1(Hazardous Substances Data)

Usage

General Description

7-Methoxy-1-naphthaleneacetic acid ethyl ester is a chemical compound with the molecular formula C14H14O3. It is an ethyl ester derivative of 7-methoxy-1-naphthaleneacetic acid, which is a compound with potential anti-inflammatory and anti-cancer properties. This chemical is commonly used in pharmaceutical research and drug development as an intermediate in the synthesis of potential pharmaceutical agents. It is known for its ability to inhibit the production of prostaglandins and leukotrienes, which are involved in the inflammatory response. Additionally, it has shown potential as an anti-cancer agent by suppressing the growth of cancer cells. Overall, 7-Methoxy-1-naphthaleneacetic acid ethyl ester is a compound with promising pharmacological properties and is being studied for its potential therapeutic applications.

InChI:InChI=1/C15H16O3/c1-3-18-15(16)9-12-6-4-5-11-7-8-13(17-2)10-14(11)12/h4-8,10H,3,9H2,1-2H3

Synthetic route

ethyl 1-hydroxy-7-methoxy-1,2,3,4-tetrahydro-1-naphthaleneacetate (99416-97-4) → ethyl 2-(7-methoxynaphthalen-1-yl)acetate (6836-21-1)

Conditions	Yield
sulfur at 215 - 225℃;	95.79%
With 1,1-Diphenylethylene; palladium on activated charcoal; 1-Methylnaphthalene at 250 - 260℃; for 3h;	81%
With 1,1-Diphenylethylene; 1-Methylnaphthalene; palladium 10% on activated carbon at 250 - 260℃; for 3h;	19.2%

ethyl (7-methoxy-1,2,3,4-tetrahydro-1-naphthalenylidene)acetate (6836-20-0) + 2-(7-methoxy-3,4-dihydro-naphthalen-1-yl)-acetic acid ethyl ester (27533-70-6) → ethyl 2-(7-methoxynaphthalen-1-yl)acetate (6836-21-1)

Conditions	Yield
With 2,3-dicyano-5,6-dichloro-p-benzoquinone In dichloromethane at 15 - 20℃;	95%

2-(7-methoxy-3,4-dihydro-naphthalen-1-yl)-acetic acid ethyl ester (27533-70-6) → ethyl 2-(7-methoxynaphthalen-1-yl)acetate (6836-21-1)

Conditions	Yield
With 2,3-dicyano-5,6-dichloro-p-benzoquinone In dichloromethane at 15 - 20℃;	91%
With 2,3-dicyano-5,6-dichloro-p-benzoquinone In dichloromethane at 25 - 30℃; for 12h;	87.3%
With 2,3-dicyano-5,6-dichloro-p-benzoquinone In dichloromethane at 15℃; Reagent/catalyst; Temperature; Solvent; Large scale;	14 kg

7-Methoxy-1-tetralone (6836-19-7) → ethyl 2-(7-methoxynaphthalen-1-yl)acetate (6836-21-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) N-isopropylcyclohexylamine, n-butyllithium / 1.) THF, hexane, -75 deg C, 15 min, 2.) THF, hexane, -78 deg C, 1.5 h 2: 81 percent / 10percent Pd/C, 1,1-diphenylethylene, 1-methylnaphthalene / 3 h / 250 - 260 °C View Scheme
Multi-step reaction with 2 steps 1.1: zinc / tert-butyl methyl ether / 55 - 60 °C 1.2: 10 - 15 °C 2.1: sulfur / 215 - 225 °C View Scheme
Multi-step reaction with 2 steps 1.1: zinc / iodine / toluene / Reflux 1.2: Reflux 1.3: 3 h / Reflux 2.1: sulfur / ethyl acetate / 10 h / 215 °C View Scheme
Multi-step reaction with 2 steps 1: sodium methylate; sodium / methanol; tetrahydrofuran / Reflux; Large scale 2: 2,3-dicyano-5,6-dichloro-p-benzoquinone / dichloromethane / 15 °C / Large scale View Scheme

4-(4-Methoxyphenyl)butyric acid (4521-28-2) → ethyl 2-(7-methoxynaphthalen-1-yl)acetate (6836-21-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: 83 percent / polyphosphoric acid / 0.12 h / 90 - 100 °C 2: 1.) N-isopropylcyclohexylamine, n-butyllithium / 1.) THF, hexane, -75 deg C, 15 min, 2.) THF, hexane, -78 deg C, 1.5 h 3: 81 percent / 10percent Pd/C, 1,1-diphenylethylene, 1-methylnaphthalene / 3 h / 250 - 260 °C View Scheme

ethyl (7-methoxy-1,2,3,4-tetrahydronaphthyliden-1-yl)acetate → ethyl 2-(7-methoxynaphthalen-1-yl)acetate (6836-21-1)

Conditions	Yield
With hydrogen sulfide In ethyl acetate

ethyl (1,2,3,4-tetrahydro-7-methoxy-1-naphthyl)acetate (27532-26-9) → ethyl 2-(7-methoxynaphthalen-1-yl)acetate (6836-21-1)

Conditions	Yield
With sulfur In ethyl acetate at 215℃; for 10h;

2-(1,2-dihydro-6-methoxynaphthalen-4-yl)acetic acid (27533-69-3) → ethyl 2-(7-methoxynaphthalen-1-yl)acetate (6836-21-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: sulfuric acid / ethanol / 12 h / 100 - 102 °C 2: 2,3-dicyano-5,6-dichloro-p-benzoquinone / dichloromethane / 12 h / 25 - 30 °C View Scheme

5-diazo-2,2-dimethyl-1,3-dioxane-4,6-dion (7270-63-5) + ethanol (64-17-5) + 2-Methoxynaphthalene (93-04-9) → (6-methoxynaphthalen-2-yl)acetic acid ethyl ester (38077-95-1) + ethyl 2-(7-methoxynaphthalen-1-yl)acetate (6836-21-1)

Conditions	Yield
Stage #1: 5-diazo-2,2-dimethyl-1,3-dioxane-4,6-dion; 2-Methoxynaphthalene With bis{rhodium[3,3'-(1,3-phenylene)bis(2,2-dimethylpropanoic acid)]}; sodium sulfate at 20℃; for 18h; Inert atmosphere; Stage #2: ethanol at 80℃; Inert atmosphere; Stage #3: With triethylamine at 80℃; for 0.25h; Inert atmosphere; Overall yield = 72 %; Overall yield = 176 mg;

ethyl 2-(7-methoxynaphthalen-1-yl)acetate (6836-21-1) → 2-(7-methoxynaphthalen-1-yl)ethan-1-ol (99416-99-6)

Conditions	Yield
With sodium tetrahydroborate; ethanol; calcium chloride In tetrahydrofuran at 5 - 20℃; Reagent/catalyst; Solvent; Temperature;	97%
With lithium aluminium tetrahydride In diethyl ether Ambient temperature;	94%

ethyl 2-(7-methoxynaphthalen-1-yl)acetate (6836-21-1) → 2-(7-methoxynaphthalen-1-yl)acetic acid (6836-22-2)

Conditions	Yield
Stage #1: ethyl 2-(7-methoxynaphthalen-1-yl)acetate With sodium hydroxide; water In methanol at 40℃; for 2h; Stage #2: With hydrogenchloride In water pH=2;	90%
In sodium hydroxide; ethanol	68%
Stage #1: ethyl 2-(7-methoxynaphthalen-1-yl)acetate With ethanol; sodium hydroxide for 2h; Reflux; Stage #2: With hydrogenchloride; water pH=1 - 2; Cooling with ice;	4.9 g
Stage #1: ethyl 2-(7-methoxynaphthalen-1-yl)acetate With water; sodium hydroxide In ethanol at 20℃; for 3h; Stage #2: With hydrogenchloride In ethanol; water

ethyl 2-(7-methoxynaphthalen-1-yl)acetate (6836-21-1) → ethyl 2-[7-methoxy(1-naphthyl)]-2-diazoacetate

Conditions	Yield
With 4-toluenesulfonyl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 0 - 20℃; Inert atmosphere;	90%

ethyl 2-(7-methoxynaphthalen-1-yl)acetate (6836-21-1) → 2-(2-methoxynaphthalen-8-yl)acetamide (138113-07-2)

Conditions	Yield
With ammonia In ethanol at -78 - 30℃;	87.6%
Multi-step reaction with 3 steps 1: sodium hydroxide; water / ethanol / 3 h / 20 °C 2: thionyl chloride / dichloromethane / 2 h / Reflux 3: ammonia / ethyl acetate; water / Cooling with ice View Scheme
With ammonium hydroxide In methanol at 40 - 50℃; for 5h;	9.3 kg

ethyl 2-(7-methoxynaphthalen-1-yl)acetate (6836-21-1) + benzoyl chloride (98-88-4) → ethyl (3-benzoyl-7-methoxy-1-naphthyl)acetate

Conditions	Yield
With aluminum (III) chloride In dichloromethane at 0 - 20℃;

ethyl 2-(7-methoxynaphthalen-1-yl)acetate (6836-21-1) → 1-(2-bromoethyl)-7-methoxy-1-naphthalene (99417-00-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: 94 percent / lithium aluminum hydride / diethyl ether / Ambient temperature 2: pyridine / 2 h 3: KBr, 18-crown-6 ether / acetone / Heating View Scheme

ethyl 2-(7-methoxynaphthalen-1-yl)acetate (6836-21-1) → 3-<2-(7-methoxy-1-naphthyl)ethyl>cyclohexanone 2,3-oxide (99417-02-4)

Conditions	Yield
Multi-step reaction with 5 steps 1: 94 percent / lithium aluminum hydride / diethyl ether / Ambient temperature 2: pyridine / 2 h 3: KBr, 18-crown-6 ether / acetone / Heating 4: 1.) Mg, 1,2-dibromoethane / 1.) ether, 1 h, 2.) ether, 5 deg C - 9 deg C, 4 h 5: 88 percent / 30percent aq. H2O2, 6 N aq. NaOH / ethanol / 3 h / 20 °C View Scheme

ethyl 2-(7-methoxynaphthalen-1-yl)acetate (6836-21-1) → 3-<2-(7-methoxy-1-naphthyl)ethyl>-2-cyclohexeneone (99439-47-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: 94 percent / lithium aluminum hydride / diethyl ether / Ambient temperature 2: pyridine / 2 h 3: KBr, 18-crown-6 ether / acetone / Heating 4: 1.) Mg, 1,2-dibromoethane / 1.) ether, 1 h, 2.) ether, 5 deg C - 9 deg C, 4 h View Scheme

ethyl 2-(7-methoxynaphthalen-1-yl)acetate (6836-21-1) → 7-methoxy-1-naphthylethyl benzenesulfonate (99417-10-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 94 percent / lithium aluminum hydride / diethyl ether / Ambient temperature 2: pyridine / 2 h View Scheme

ethyl 2-(7-methoxynaphthalen-1-yl)acetate (6836-21-1) → 2-(7-methoxynaphth-1-yl)ethylamine (138113-09-4)

Conditions	Yield
Multi-step reaction with 5 steps 1: sodium hydroxide; water / ethanol / 3 h / 20 °C 2: thionyl chloride / dichloromethane / 2 h / Reflux 3: ammonia / ethyl acetate; water / Cooling with ice 4: triethylamine; trifluoroacetic anhydride / tetrahydrofuran / 20 °C / Cooling with ice 5: hydrogen; ammonia / ethanol; water / 12 h / 60 °C / 228015 Torr / Autoclave View Scheme
Multi-step reaction with 4 steps 1: sodium tetrahydroborate; calcium chloride; ethanol / tetrahydrofuran / 5 - 20 °C 2: triethylamine / dichloromethane / 15 °C 3: dimethyl sulfoxide / 50 °C 4: sodium hydroxide; methanol / 18 h / 40 °C View Scheme

ethyl 2-(7-methoxynaphthalen-1-yl)acetate (6836-21-1) → agomelatine (138112-76-2)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: sodium hydroxide; water / ethanol / 3 h / 20 °C 2.1: thionyl chloride / dichloromethane / 2 h / Reflux 3.1: ammonia / ethyl acetate; water / Cooling with ice 4.1: triethylamine; trifluoroacetic anhydride / tetrahydrofuran / 20 °C / Cooling with ice 5.1: hydrogen; ammonia / ethanol; water / 12 h / 60 °C / 228015 Torr / Autoclave 6.1: pyridine / 40 °C 6.2: 20 °C / Cooling with ice View Scheme
Multi-step reaction with 5 steps 1: sodium tetrahydroborate; calcium chloride; ethanol / tetrahydrofuran / 5 - 20 °C 2: triethylamine / dichloromethane / 15 °C 3: dimethyl sulfoxide / 50 °C 4: sodium hydroxide; methanol / 18 h / 40 °C 5: toluene / 3 h / 40 °C View Scheme

ethyl 2-(7-methoxynaphthalen-1-yl)acetate (6836-21-1) → (7-methoxy-1-naphthyl)acetonitrile (138113-08-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: sodium hydroxide; water / ethanol / 3 h / 20 °C 2: thionyl chloride / dichloromethane / 2 h / Reflux 3: ammonia / ethyl acetate; water / Cooling with ice 4: triethylamine; trifluoroacetic anhydride / tetrahydrofuran / 20 °C / Cooling with ice View Scheme

ethyl 2-(7-methoxynaphthalen-1-yl)acetate (6836-21-1) → (7-methoxy-1-naphthyl)acetic acid chloride (6836-23-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydroxide; water / ethanol / 3 h / 20 °C 2: thionyl chloride / dichloromethane / 2 h / Reflux View Scheme

ethyl 2-(7-methoxynaphthalen-1-yl)acetate (6836-21-1) → 2-(7-methoxynaphthalen-1-yl)ethyl methanesulphonate (185336-04-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium tetrahydroborate; calcium chloride; ethanol / tetrahydrofuran / 5 - 20 °C 2: triethylamine / dichloromethane / 15 °C View Scheme

ethyl 2-(7-methoxynaphthalen-1-yl)acetate (6836-21-1) → N-formyl-N-(2-(7-methoxynaphthalen-1-yl)ethyl)formamide (1424944-39-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium tetrahydroborate; calcium chloride; ethanol / tetrahydrofuran / 5 - 20 °C 2: triethylamine / dichloromethane / 15 °C 3: dimethyl sulfoxide / 50 °C View Scheme

ethyl 2-(7-methoxynaphthalen-1-yl)acetate (6836-21-1) → (3-benzoyl-7-methoxy-1-naphthyl)acetic acid

Conditions	Yield
Multi-step reaction with 2 steps 1.1: aluminum (III) chloride / dichloromethane / 0 - 20 °C 2.1: lithium hydroxide; water / 1,4-dioxane / 3 h / 20 °C 2.2: pH ~ 2 View Scheme

ethyl 2-(7-methoxynaphthalen-1-yl)acetate (6836-21-1) → (3-benzoyl-7-methoxy-1-naphthyl)-N,N-dipropylacetamide (960232-20-6)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: aluminum (III) chloride / dichloromethane / 0 - 20 °C 2.1: lithium hydroxide; water / 1,4-dioxane / 3 h / 20 °C 2.2: pH ~ 2 3.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 20 °C View Scheme

ethyl 2-(7-methoxynaphthalen-1-yl)acetate (6836-21-1) → C24H22O3S

Conditions	Yield
Multi-step reaction with 2 steps 1: 1,8-diazabicyclo[5.4.0]undec-7-ene; 4-toluenesulfonyl azide / acetonitrile / 0 - 20 °C / Inert atmosphere 2: dichloromethane / 24 h / Irradiation; Sealed tube View Scheme

Upstream product

• 6836-20-0 ethyl (7-methoxy-1,2,3,4-tetrahydro-1-naphthalenylidene)acetate 
• 27533-70-6 2-(7-methoxy-3,4-dihydro-naphthalen-1-yl)-acetic acid ethyl ester 
• 7270-63-5 5-diazo-2,2-dimethyl-1,3-dioxane-4,6-dion 
• 64-17-5 ethanol 
• 93-04-9 2-Methoxynaphthalene 
• 27533-69-3 2-(1,2-dihydro-6-methoxynaphthalen-4-yl)acetic acid 
• 27532-26-9 ethyl (1,2,3,4-tetrahydro-7-methoxy-1-naphthyl)acetate 
• 4521-28-2 4-(4-Methoxyphenyl)butyric acid 
• 6836-19-7 7-Methoxy-1-tetralone 
• 99416-97-4 ethyl 1-hydroxy-7-methoxy-1,2,3,4-tetrahydro-1-naphthaleneacetate 

Downstream Products

• 138113-08-3 (7-methoxy-1-naphthyl)acetonitrile 
• 960232-20-6 (3-benzoyl-7-methoxy-1-naphthyl)-N,N-dipropylacetamide 
• 6836-23-3 (7-methoxy-1-naphthyl)acetic acid chloride 
• 138113-07-2 2-(2-methoxynaphthalen-8-yl)acetamide 
• 138112-76-2 agomelatine 
• 138113-09-4 2-(7-methoxynaphth-1-yl)ethylamine 
• 6836-22-2 2-(7-methoxynaphthalen-1-yl)acetic acid 
• 99417-10-4 7-methoxy-1-naphthylethyl benzenesulfonate 
• 99439-47-1 3-<2-(7-methoxy-1-naphthyl)ethyl>-2-cyclohexeneone 
• 99416-99-6 2-(7-methoxynaphthalen-1-yl)ethan-1-ol 

Relevant articles and documents

A Practical synthesis of (7-methoxynaphth-l-yl)acetic acid

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Modular Synthesis of Arylacetic Acid Esters, Thioesters, and Amides from Aryl Ethers via Rh(II)-Catalyzed Diazo Arylation

One-pot formation of arylacetic acid esters, thioesters, and amides via Rh(II)-catalyzed arylation of a Meldrum's acid-derived diazo reagent with electron-rich arenes is described. The methodology was used to efficiently synthesize an anticancer compound.

PROCESS FOR THE PREPARATION OF AGOMELATINE

The present invention relates to a process for the manufacture of N-[2-(7-methoxy-1-naphthalenyl) ethyl]acetamide (Agomelatine) with improved yield and reduced level of N- acetyl-N-[2-(7-methoxy-1-naphthalenyl) ethyl]acetamide impurity.