38464-04-9

Usage

Uses

Used in Pharmaceutical Research:
3,4-Diethoxyphenylacetic acid is used as a research compound for its potential pharmacological properties, particularly in the development of new drugs targeting inflammation and pain.
Used in Organic Synthesis:
3,4-Diethoxyphenylacetic acid is utilized as a key intermediate in the synthesis of various organic compounds, contributing to the creation of novel chemical entities with potential applications in different fields.
Used in Anti-inflammatory and Analgesic Applications:
3,4-Diethoxyphenylacetic acid is used as an anti-inflammatory and analgesic agent, leveraging its potential to alleviate pain and reduce inflammation, which is crucial in the management of various conditions and diseases.
Used in Neurodegenerative Disease Treatment:
3,4-Diethoxyphenylacetic acid is used in the research and development of treatments for neurodegenerative diseases, given its potential to impact the progression of such conditions and improve patient outcomes.

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

• 2050-46-6 1,2-diethoxybenzene 
• 1137-71-9 1-(3,4-diethoxyphenyl)ethanone 
• 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 
• 27472-21-5 3,4-diethoxyphenylacetonitrile 

Downstream Products

• 139355-83-2 2-<(3,4-diethoxyphenyl)methyl>-4H-3,1-benzoxazin-4-one 
• 1104307-63-2 2-(2-methoxy-2-oxoethyl)phenyl 2-(3,4-diethoxyphenyl)acetate 
• 1104308-02-2 2-(2-ethoxy-2-oxoethyl)phenyl 2-(3,4-diethoxyphenyl)acetate 
• 61381-04-2 2-(3,4-diethoxyphenyl)ethylamine 
• 6298-46-0 N-(3,4-diethoxyphenylacetyl)-β-(3,4-diethoxyphenyl)ethylamine 
• 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 
• 92157-09-0 methyl 2-(3,4-diethoxyphenyl)acetate 
• 1338603-28-3 2-(3,4-diethoxyphenyl)-N-(5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1,3,4-thiadiazol-2-yl)acetamide 

Relevant academic research and scientific papers

Novel method for preparing drotaverine hydrochloride intermediate

The invention discloses a novel method for preparing a drotaverine hydrochloride intermediate, belonging to the technical field of medicine synthesis. The preparation method comprises the following steps: preparing an intermediate 3,4-diethoxyphenylacetic acid with 1,2-diethoxybenzene as a raw material, and preparing the intermediate 3,4-diethoxyphenylacetamide with 3,4-diethoxyphenylacetic acid as a raw material. According to the novel process for preparing the drotaverine hydrochloride intermediate, a method for directly preparing 3,4-diethoxyphenylacetic acid and 3,4-diethoxyphenylethylamine is adopted, and a process for preparing 3,4-diethoxyphenylacetonitrile is avoided, so a reaction step of using sodium cyanide is avoided.

Novel preparation method of drotaverine hydrochloride intermediate

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.

Substituted indolinones, their manufacture and their use as medicaments

The present invention relates to substituted indolinones of general formula wherein R1to R6and X are defined as in claim 1, the isomers and the salts thereof, in particular the physiologically acceptable salts thereof which have valuable pharmacological properties, especially an inhibitory effect on various receptor-tyrosine kinases, and cycline/CDK complexes as well as on the proliferation of endothelial cells and various tumor cells, pharmaceutical compositions containing these compounds, their use and processes for preparing them.

Process for the manufacture of pure isoquinoline derivatives

In the production of perparine or papaverine and their hydrochlorides, the formation of impurities in the reaction mixture is suppressed by fractionating a 3,4-di-R-benzyl-cyanide in the presence of an organic base (e.g. pyridine, dimethylformamide, ethylenediamine or triethylamine) followed by hydrogenation with a Raney-nickel catalyst treated with aqueous ammonium carbonate solution. R is methoxy or ethoxy.

3(2H)-Isoquinolones therapeutic process

New 2-substituted-3(2H)-isoquinolones and 2-substituted-3-alkoxyisoquinolines are disclosed. They are orally active hypotensives and peripheral vasodilators with an extended duration of action. Representative embodiments of this invention are 6,7-dimethoxy-2-methyl-1-veratryl-3(2H)-isoquinolone hydrochloride, 2-allyl-6,7-dimethoxy-1-veratryl-3(2H)-isoquinolone hydrochloride, 2-cyclopropyl-6,7-dimethoxy-1-veratryl-3(2H)-isoquinolone hydrochloride, 2-amino-6,7-dimethoxy-1-veratryl-3(2H)-isoquinolone hydrochloride, and 3-ethoxy-6,7-dimethoxy-1-veratrylisoquinoline.