38464-04-9

Basic information

• Product Name: 3,4-Diethoxyphenylacetic acid
• Synonyms: ART-CHEM-BB B006522;3,4-diethoxybenzeneacetic acid;3,4-Diethyloxy;2-(3,4-BIS(HYDROXYMETHYL)PHENYL)ACETIC ACID;(3,4-diethoxyphenyl)acetic acid(SALTDATA: FREE);2-(3,4-diethoxyphenyl)ethanoic acid;RARECHEM AL BO 0610;VITAS-BB TBB000357
• CAS NO: 38464-04-9
• Molecular Formula: C₁₂H₁₆O₄
• Molecular Weight: 224.25
• EINECS: 253-957-3
• Product Categories: Acetics acid and esters
• Mol File: 38464-04-9.mol
• Article Data: 5

Chemical Properties

• Melting Point: 77-79°C
• Boiling Point: 357.2 °C at 760 mmHg
• Flash Point: 134.1 °C
• Appearance: White solid
• Density: 1.133 g/cm₃
• Vapor Pressure: 1.01E-05mmHg at 25°C
• Refractive Index: 1.518
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: soluble in Methanol
• PKA: 4.36±0.10(Predicted)
• CAS DataBase Reference: 3,4-Diethoxyphenylacetic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 3,4-Diethoxyphenylacetic acid(38464-04-9)
• EPA Substance Registry System: 3,4-Diethoxyphenylacetic acid(38464-04-9)

Safety Data

• Hazard Codes: Xi
• HazardClass: IRRITANT
• Hazardous Substances Data: 38464-04-9(Hazardous Substances Data)

Usage

General Description

3,4-Diethoxyphenylacetic acid is a chemical compound with the molecular formula C12H16O4. It is a derivative of phenylacetic acid, with two ethoxy (C2H5O) groups attached to the phenyl ring at the 3 and 4 positions. 3,4-Diethoxyphenylacetic acid is often used in organic synthesis and pharmaceutical research due to its potential pharmacological properties. It has been studied for its potential as an anti-inflammatory and analgesic agent, and it has also been investigated for its role in the treatment of neurodegenerative diseases. 3,4-Diethoxyphenylacetic acid is a promising candidate for drug development and further research into its biological activities.

InChI:InChI=1/C12H16O4/c1-3-15-10-6-5-9(8-12(13)14)7-11(10)16-4-2/h5-7H,3-4,8H2,1-2H3,(H,13,14)

Synthetic route

ethyl 2-(3,4-diethoxyphenyl)acetate (69373-87-1) → 3,4-diethoxy-phenyl-acetic acid (38464-04-9)

Conditions	Yield
With sodium hydroxide In 1,4-dioxane at 50 - 60℃;	95.9%
With water; sodium hydroxide In tetrahydrofuran at 50 - 60℃;	88%

methyl 2-(3,4-diethoxyphenyl)acetate (92157-09-0) → 3,4-diethoxy-phenyl-acetic acid (38464-04-9)

Conditions	Yield
With sodium hydroxide In 1,4-dioxane at 50 - 60℃;	93.5%
With potassium hydroxide

1-(3,4-diethoxyphenyl)ethanone (1137-71-9) → 3,4-diethoxy-phenyl-acetic acid (38464-04-9)

Conditions	Yield
Stage #1: 1-(3,4-diethoxyphenyl)ethanone With morpholine; sulfur at 110 - 120℃; for 18h; Stage #2: With sodium hydroxide In water at 100℃; for 8h;	73%

diethyl sulfate (64-67-5) + 3,4-dihydroxyphenylacetate (102-32-9) → 3,4-diethoxy-phenyl-acetic acid (38464-04-9)

Conditions	Yield
With barium dihydroxide In water at 20 - 40℃; for 4h;	42%

3,4-diethoxyphenylacetonitrile (27472-21-5) → 3,4-diethoxy-phenyl-acetic acid (38464-04-9)

Conditions	Yield
With potassium hydroxide
With sodium hydroxide

ethyl 2-(3,4-diethoxyphenyl)-2-oxoacetate (53017-34-8) → 3,4-diethoxy-phenyl-acetic acid (38464-04-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: palladium; acetic acid; sulfuric acid / weiteres Reagens: Bromwasserstoff View Scheme
Multi-step reaction with 2 steps 1: hydrogenchloride; hydrogen; palladium 10% on activated carbon / ethanol / 15 h / 60 °C 2: sodium hydroxide; water / tetrahydrofuran / 50 - 60 °C View Scheme

1,2-diethoxy-4-chloromethyl-benzene (27472-20-4) → 3,4-diethoxy-phenyl-acetic acid (38464-04-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: benzene 2: aq.-ethanolic KOH-solution View Scheme

1-bromo-3,4-dihydroxybenzene (17345-77-6) → 3,4-diethoxy-phenyl-acetic acid (38464-04-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: potassium hydroxide / acetonitrile / 70 - 80 °C 2: potassium acetate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane / 90 - 100 °C 3: potassium dihydrogenphosphate / 1,4-dioxane; water / 90 - 100 °C 4: sodium hydroxide / 1,4-dioxane / 50 - 60 °C View Scheme
Multi-step reaction with 4 steps 1: potassium hydroxide / acetonitrile / 70 - 80 °C 2: potassium acetate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane-d8 / 90 - 100 °C 3: potassium dihydrogenphosphate / 1,4-dioxane-d8 / 90 - 100 °C 4: sodium hydroxide / 1,4-dioxane / 50 - 60 °C View Scheme

4-bromo-1,2-diethoxybenzene (53207-08-2) → 3,4-diethoxy-phenyl-acetic acid (38464-04-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium acetate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane / 90 - 100 °C 2: potassium dihydrogenphosphate / 1,4-dioxane; water / 90 - 100 °C 3: sodium hydroxide / 1,4-dioxane / 50 - 60 °C View Scheme
Multi-step reaction with 3 steps 1: potassium acetate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane-d8 / 90 - 100 °C 2: potassium dihydrogenphosphate / 1,4-dioxane-d8 / 90 - 100 °C 3: sodium hydroxide / 1,4-dioxane / 50 - 60 °C View Scheme

3,4-diethoxyphenylboronic acid (279262-08-7) → 3,4-diethoxy-phenyl-acetic acid (38464-04-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium dihydrogenphosphate / 1,4-dioxane-d8 / 90 - 100 °C 2: sodium hydroxide / 1,4-dioxane / 50 - 60 °C View Scheme

2-(3,4-diethoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1005009-95-9) → 3,4-diethoxy-phenyl-acetic acid (38464-04-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium dihydrogenphosphate / 1,4-dioxane; water / 90 - 100 °C 2: sodium hydroxide / 1,4-dioxane / 50 - 60 °C View Scheme

1,2-diethoxybenzene (2050-46-6) → 3,4-diethoxy-phenyl-acetic acid (38464-04-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: zinc(II) chloride / dichloromethane / 1 h / 0 - 20 °C 2.1: sulfur; morpholine / 18 h / 110 - 120 °C 2.2: 8 h / 100 °C View Scheme
Multi-step reaction with 3 steps 1.1: aluminum (III) chloride / toluene / 0.25 h / -10 - -5 °C 1.2: 1 h / 20 °C 2.1: hydrogenchloride; hydrogen; palladium 10% on activated carbon / ethanol / 15 h / 60 °C 3.1: sodium hydroxide; water / tetrahydrofuran / 50 - 60 °C View Scheme

2-(3,4-diethoxyphenyl)ethylamine (61381-04-2) + 3,4-diethoxy-phenyl-acetic acid (38464-04-9) → N-(3,4-diethoxyphenylacetyl)-β-(3,4-diethoxyphenyl)ethylamine (6298-46-0)

Conditions	Yield
at 180 - 190℃; Inert atmosphere;	95%
at 100 - 120℃; Inert atmosphere;	93%
at 180 - 192℃;

3,4-diethoxy-phenyl-acetic acid (38464-04-9) → 2-(3,4-diethoxyphenyl)acetamide (526190-09-0)

Conditions	Yield
Stage #1: 3,4-diethoxy-phenyl-acetic acid With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 10 - 20℃; for 1h; Stage #2: With hydroxylamine In tetrahydrofuran at 40 - 50℃; for 1h;	89%
Multi-step reaction with 2 steps 1: thionyl chloride / dichloromethane 2: ammonia / tetrahydrofuran View Scheme

methyl (2-hydroxyphenyl)acetate (22446-37-3) + 3,4-diethoxy-phenyl-acetic acid (38464-04-9) → 2-(2-methoxy-2-oxoethyl)phenyl 2-(3,4-diethoxyphenyl)acetate (1104307-63-2)

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane Reflux;	82%

3,4-diethoxy-phenyl-acetic acid (38464-04-9) + ethyl 2-(2-hydroxyphenyl)acetate (41873-65-8) → 2-(2-ethoxy-2-oxoethyl)phenyl 2-(3,4-diethoxyphenyl)acetate (1104308-02-2)

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane Reflux;	81%

3,4-diethoxy-phenyl-acetic acid (38464-04-9) + 2-(pyrimidin-5-yl)phenol → 2-(pyrimidin-5-yl)phenyl 2-(3,4-diethoxyphenyl)acetate

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane; N,N-dimethyl-formamide at 20℃; for 12h; Sealed tube;	68%

N,1-dihydroxy-2,3-dihydro-1H-indene-4-carboximidamide (1093827-51-0) + 3,4-diethoxy-phenyl-acetic acid (38464-04-9) → 4-(5-(3,4-diethoxybenzyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-ol (1307230-43-8)

Conditions	Yield
Stage #1: 3,4-diethoxy-phenyl-acetic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 2h; Stage #2: N,1-dihydroxy-2,3-dihydro-1H-indene-4-carboximidamide In N,N-dimethyl-formamide at 20 - 80℃; for 18h;	62%

(R)-tert-butyl 4-(N-hydroxycarbamimidoyl)-2,3-dihydro-1H-inden-1-ylcarbamate (1306763-32-5) + 3,4-diethoxy-phenyl-acetic acid (38464-04-9) → (R)-tert-butyl 4-(5-(3,4-diethoxybenzyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-ylcarbamate (1307231-06-6)

Conditions	Yield
Stage #1: 3,4-diethoxy-phenyl-acetic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 2h; Stage #2: (R)-tert-butyl 4-(N-hydroxycarbamimidoyl)-2,3-dihydro-1H-inden-1-ylcarbamate In N,N-dimethyl-formamide at 20 - 80℃; for 18h;	58%

3,4-diethoxy-phenyl-acetic acid (38464-04-9) → 4,5-diethoxy-2-nitro-phenylacetic acid (329083-17-2)

Conditions	Yield
With nitric acid; acetic acid In water at 15 - 40℃; for 0.5h;	57%

3,4-diethoxy-phenyl-acetic acid (38464-04-9) + anthranilic acid (118-92-3) → 2-<(3,4-diethoxyphenyl)methyl>-4H-3,1-benzoxazin-4-one (139355-83-2)

Conditions	Yield
With trichlorophosphate for 5h; Heating;	6%

3,4-diethoxy-phenyl-acetic acid (38464-04-9) + 3,4-methylenedioxyphenylethylamine (1484-85-1) → (3,4-diethoxy-phenyl)-acetic acid homopiperonylamide

Conditions	Yield
at 200℃;

2-(tert-butoxycarbonylamino)-3-phenylpropionic acid (4530-18-1) + 3,4-diethoxy-phenyl-acetic acid (38464-04-9) + phenyl isocyanatoformate (5843-43-6) → 7-benzyl-1-[3-(3,4-dimethoxy-phenyl)-propyl]-[1,3,5]triazepane-2,4-dione

Conditions	Yield
Multistep reaction.;

3,4-diethoxy-phenyl-acetic acid (38464-04-9) → ethaverine (486-47-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: 180 - 192 °C 2: phosphoryl chloride; benzene 3: palladium/charcoal; diisopropylbenzene View Scheme

3,4-diethoxy-phenyl-acetic acid (38464-04-9) → 1-(3',4'-diethoxy-benzyl)-6,7-diethoxy-3,4-dihydro-isoquinoline (861-27-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 180 - 192 °C 2: phosphoryl chloride; benzene View Scheme

3,4-diethoxy-phenyl-acetic acid (38464-04-9) + 2-hydroxyresorcinol (87-66-1) → C18H20O6

Conditions	Yield
With boron trifluoride diethyl etherate at 80 - 85℃; for 3h;

3,4-diethoxy-phenyl-acetic acid (38464-04-9) → (3,4-diethoxy-phenyl)-acetyl chloride (139036-00-3)

Conditions	Yield
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0℃; for 1h;
With thionyl chloride at 90℃;
With thionyl chloride In dichloromethane

3,4-diethoxy-phenyl-acetic acid (38464-04-9) → 1-(4-chloro-phenyl)-6,7-diethoxy-2-[4-methyl-2-(3-morpholin-4-yl-propoxy)-phenyl]-1,4-dihydro-2H-isoquinolin-3-one trifluoroacetate (1313359-85-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 1 h / 0 °C 2: di-tert-butyl-diazodicarboxylate / dichloromethane / 3 h / 20 °C View Scheme

N-(5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1,3,4-thiadiazol)-2-amine (1152573-49-3) + 3,4-diethoxy-phenyl-acetic acid (38464-04-9) → 2-(3,4-diethoxyphenyl)-N-(5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1,3,4-thiadiazol-2-yl)acetamide (1338603-28-3)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane Reflux;

methanol (67-56-1) + 3,4-diethoxy-phenyl-acetic acid (38464-04-9) → methyl 2-(3,4-diethoxyphenyl)acetate (92157-09-0)

Conditions	Yield
With sulfuric acid Reflux;

3,4-diethoxy-phenyl-acetic acid (38464-04-9) → C19H20N2O3 (1345540-08-0)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sulfuric acid / Reflux 2.1: tin(ll) chloride / 20 °C 3.1: hydrazine hydrate / ethanol / 3 h / 150 °C 3.2: 0.5 h / Reflux View Scheme

3,4-diethoxy-phenyl-acetic acid (38464-04-9) → C19H19ClN2O3 (474069-98-2)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sulfuric acid / Reflux 2.1: tin(ll) chloride / 20 °C 3.1: hydrazine hydrate / ethanol / 3 h / 150 °C 3.2: 0.5 h / Reflux View Scheme

3,4-diethoxy-phenyl-acetic acid (38464-04-9) → C19H19ClN2O3 (1345540-12-6)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sulfuric acid / Reflux 2.1: tin(ll) chloride / 20 °C 3.1: hydrazine hydrate / ethanol / 3 h / 150 °C 3.2: 0.5 h / Reflux View Scheme

3,4-diethoxy-phenyl-acetic acid (38464-04-9) → 1-(2-benzo[b]thienyl)-7,8-diethoxy-3,5-dihydro-4H-2,3-benzodiazepin-4-one

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sulfuric acid / Reflux 2.1: tin(ll) chloride / 20 °C 3.1: hydrazine hydrate / ethanol / 3 h / 150 °C 3.2: 0.5 h / Reflux View Scheme

Upstream product

• 27472-21-5 3,4-diethoxyphenylacetonitrile 
• 1137-71-9 1-(3,4-diethoxyphenyl)ethanone 
• 2050-46-6 1,2-diethoxybenzene 
• 1005009-95-9 2-(3,4-diethoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 
• 279262-08-7 3,4-diethoxyphenylboronic acid 
• 53207-08-2 4-bromo-1,2-diethoxybenzene 
• 17345-77-6 1-bromo-3,4-dihydroxybenzene 
• 64-67-5 diethyl sulfate 
• 102-32-9 3,4-dihydroxyphenylacetate 
• 27472-20-4 1,2-diethoxy-4-chloromethyl-benzene 
• 53017-34-8 ethyl 2-(3,4-diethoxyphenyl)-2-oxoacetate 
• 69373-87-1 ethyl 2-(3,4-diethoxyphenyl)acetate 
• 92157-09-0 methyl 2-(3,4-diethoxyphenyl)acetate 

Downstream Products

• 61381-04-2 2-(3,4-diethoxyphenyl)ethylamine 
• 6298-46-0 N-(3,4-diethoxyphenylacetyl)-β-(3,4-diethoxyphenyl)ethylamine 
• 1446490-45-4 N-(4-(4-bromophenyl)thiazol-2-yl)-2-(3,4-diethoxyphenyl)acetamide 
• 1446490-35-2 2-(3,4-diethoxyphenyl)-N-(4-phenylthiazol-2-yl)acetamide 
• 1307231-06-6 (R)-tert-butyl 4-(5-(3,4-diethoxybenzyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-ylcarbamate 
• 1307230-43-8 4-(5-(3,4-diethoxybenzyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-ol 
• 1243290-17-6 N-(1-(1H-benzo[d][1,2,3]triazol-1-yl)-2,2-dimethylpropyl)-2-(3,4-diethoxyphenyl)acetamide 
• 1345539-92-5 C₂₂H₂₂O₅S 
• 1345539-90-3 C₂₀H₂₁ClO₅ 
• 1345539-88-9 C₂₀H₂₁ClO₅ 
• 1345539-85-6 C₂₀H₂₂O₅ 
• 1345540-12-6 C₁₉H₁₉ClN₂O₃ 
• 474069-98-2 C₁₉H₁₉ClN₂O₃ 
• 1345540-08-0 C₁₉H₂₀N₂O₃ 

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The invention discloses a novel preparation method of a drotaverine hydrochloride intermediate. The preparation method comprises the steps that 1, 4-bromopyrocatechol serves as the raw material and issubjected to an ethylation reaction under the action of iodoethane or diethyl sulfate, and 1,2-diethoxy-4-bromobenzene is prepared; 2, 1,2-diethoxy-4-bromobenzene is subjected to a Suzuki-Miyaura coupling reaction and reacts with ethyl bromoacetate or methyl bromoacetate to prepare 3,4-diethoxyphenylaceticacid ester; 3, 3,4-diethoxyphenylaceticacid is hydrolyzed to prepare 3,4-diethoxyphenylaceticacid; 4, 3,4-diethoxyphenylaceticacid ester and ammonia are prepared into 3,4-diethoxyphenylacetamide; 5, 3,4-diethoxyphenylacetamide is reduced to prepare 3,4-diethoxyphenethylamine. The direct preparation method is used; in the process of preparing 3,4-diethoxyphenyl acetonitrile, application of sodium cyanide is avoided; when 3,4-diethoxyphenethylamine is prepared, lithium aluminium hydride isused for reduction, and a pressurized hydrogenation method is prevented from being used, so that the problems about safety and environment pollution are effectively solved, the process is simple andeasy to implement, and the practicality is high.

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