60758-86-3

Basic information

• Product Name: Benzonitrile, 3-ethoxy-4-Methoxy-
• Synonyms: Benzonitrile, 3-ethoxy-4-Methoxy-;3-ethoxy-4-Methoxybenzonitrile;3-Ethoxy-4-Methoxy benzontrile
• CAS NO: 60758-86-3
• Molecular Formula: C₁₀H₁₁NO₂
• Molecular Weight: 177.19984
• Product Categories: apremilast intermediates;Apremilast
• Mol File: 60758-86-3.mol
• Article Data: 11

Chemical Properties

• Melting Point: 70℃
• Boiling Point: 281.9±25.0℃ (760 Torr)
• Flash Point: 109.2±16.4℃
• Appearance: /
• Density: 1.09±0.1 g/cm3 (20 ºC 760 Torr)
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: soluble in Methanol
• CAS DataBase Reference: Benzonitrile, 3-ethoxy-4-Methoxy-(CAS DataBase Reference)
• NIST Chemistry Reference: Benzonitrile, 3-ethoxy-4-Methoxy-(60758-86-3)
• EPA Substance Registry System: Benzonitrile, 3-ethoxy-4-Methoxy-(60758-86-3)

Safety Data

• RIDADR: 3439
• HazardClass: 6.1
• PackingGroup: III
• Hazardous Substances Data: 60758-86-3(Hazardous Substances Data)

Usage

Uses

3-Ethoxy-4-methoxy benzonitrile can be used as organic synthesis intermediate and pharmaceutical intermediate, mainly used in laboratory research and development process and chemical production process.

Synthesis

In a 100 ml flask in the, adding 3-hydroxy-4-methoxy phenyl nitrile 10g (67.11mmol), bromoethane 25 ml (335.2mmol), potassium carbonate 10.25g, dimethyl formamide 50 ml, heating and stirring to 100 °C. TLC monitoring reaction, reaction 8h, stop heating. Natural cooling to room temperature, water 100 ml, the ethyl acetate extraction, the organic phase is dried with anhydrous sodium sulfate, ethyl acetate solvent turns on lathe does the white solid obtained 11.09g.

Synthetic route

3-ethoxy-4-methoxybenzaldehyde (1131-52-8) → 3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3)

Conditions	Yield
With hydroxylamine hydrochloride In acetonitrile at 5 - 84℃; Product distribution / selectivity;	95.5%
Multi-step reaction with 2 steps 1: hydroxylamine hydrochloride, sodium hydroxide / aq. ethanol; H2O / Ambient temperature 2: acetic anhydride / Heating View Scheme
With hydroxylamine hydrochloride In acetonitrile Reflux;
With hydroxylamine hydrochloride In formic acid at 85 - 90℃; Temperature;	600 g

ethyl bromide (74-96-4) + 2-methoxy-5-cyanophenol (52805-46-6) → 3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 8h;	94%
With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 8h; Solvent; Concentration; Temperature; Industrial scale;	94%
Stage #1: 2-methoxy-5-cyanophenol With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.583333h; Stage #2: ethyl bromide In N,N-dimethyl-formamide at 0 - 20℃;
With potassium carbonate In acetone Reflux;

3-ethoxy-4-hydroxybenzonitrile (60758-79-4) + methyl iodide (74-88-4) → 3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3)

Conditions	Yield
With potassium carbonate In acetone for 4h; Reflux;	89.3%

1-methyl-4-nitrosobenzene (623-11-0) + (+/-)-3-ethoxy-2'-chloro-4-methoxy-benzoin-seqtrans-oxime + benzenesulfonyl chloride (98-09-9) → 3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3) + 2-chloro-benzaldehyde (89-98-5)

3-ethoxy-4-methoxybenzaldoxime (1956-36-1) → 3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3)

Conditions	Yield
With acetic anhydride Heating;

4-methoxy-3-ethoxy-benzaldehyde-oxime → 3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3)

Conditions	Yield
With acetic anhydride

3-ethoxy-4-methoxy-benzoic acid amide (247569-89-7) → 3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3)

Conditions	Yield
With trichlorophosphate In pyridine

4-ethoxy-3-methoxy-benzoic acid amide (247569-93-3) → 4-ethoxy-3-methoxybenzonitrile (81259-56-5) + 3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3)

3-methoxy-4-(2-methoxyethoxy)benzamide (247569-95-5) → 3-methoxy-4-(2-methoxyethoxy)benzonitrile (247569-96-6) + 3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3)

3-benzyloxy-4-methoxybenzamide (247570-05-4) → 3-benzyloxy-4-methoxybenzonitrile (52805-37-5) + 3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3)

isovanillin (621-59-0) → 3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: formic acid; hydroxylamine hydrochloride; sodium formate / 3 h / 125 °C 2: potassium carbonate / N,N-dimethyl-formamide View Scheme
Multi-step reaction with 2 steps 1: sodium formate; hydroxylamine hydrochloride / formic acid / 5 h / 85 °C 2: potassium carbonate / N,N-dimethyl-formamide / 8 h / 100 °C View Scheme
Multi-step reaction with 2 steps 1: formic acid; sodium formate; hydroxylamine hydrochloride / 5 h / 85 °C / Industrial scale 2: potassium carbonate / N,N-dimethyl-formamide / 8 h / 100 °C / Industrial scale View Scheme

2-methoxy-5-cyanophenol (52805-46-6) + ethyl halide → 3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide

4-hydroxy-3-ethoxybenzaldehyde (121-32-4) → 3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydroxylamine hydrochloride / acetonitrile / 4 h / Reflux 2: potassium carbonate / acetone / 4 h / Reflux View Scheme

ethyl 3-methoxy-4-(2-methoxyethoxy)benzoate (196194-41-9) → 3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3)

4-hydroxy-3-methoxybenzoic acid methyl ester (3943-74-6) → 3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3)

3-methoxy-4-(2-methoxyethoxy)benzoic acid (247569-94-4) → 3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3)

ethyl 4-cyclobutylmethoxy-3-methoxybenzoate (247569-98-8) → 3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3)

Conditions	Yield
Multi-step reaction with 3 steps 2: N-methyl-acetamide; dichloromethane 3: trichlorophosphate / pyridine View Scheme

3-hydroxy-4-methoxybenzoate (6702-50-7) → 3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: potassium carbonate / N-methyl-acetamide 2: methanol 3: N-methyl-acetamide; dichloromethane 4: trichlorophosphate / pyridine View Scheme

ethyl vanillate (617-05-0) → 3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3)

Conditions	Yield
Multi-step reaction with 4 steps 2: methanol 3: N-methyl-acetamide; dichloromethane 4: trichlorophosphate / pyridine View Scheme

4-ethoxy-3-methoxybenzoic acid (3535-30-6) → 3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3)

3-methoxy-4-hydroxybenzoic acid (121-34-6) → 3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3)

Isovanillic acid (645-08-9) → 3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: sulfuric acid / methanol 2: potassium carbonate / N-methyl-acetamide 3: methanol 4: N-methyl-acetamide; dichloromethane 5: trichlorophosphate / pyridine View Scheme

3-ethoxy-4-methoxybenzoic acid (2651-55-0) → 3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: N-methyl-acetamide; dichloromethane 2: trichlorophosphate / pyridine View Scheme

methyl 3-(benzyloxy)-4-methoxy-benzoate (57535-57-6) → 3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3)

Conditions	Yield
Multi-step reaction with 3 steps 2: N-methyl-acetamide; dichloromethane 3: trichlorophosphate / pyridine View Scheme

4-ethoxy-3-methoxybenzoic acid methyl ester (3535-24-8) → 3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3)

3-ethoxy-4-methoxybenzoic acid methyl ester (97966-31-9) → 3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: methanol 2: N-methyl-acetamide; dichloromethane 3: trichlorophosphate / pyridine View Scheme

dimethylsulfone (67-71-0) + 3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3) → 1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethen-1-amine (1450657-31-4)

Conditions	Yield
Stage #1: dimethylsulfone With n-butyllithium In tetrahydrofuran; hexane at -5 - 0℃; for 2h; Stage #2: 3-ethoxy-4-methoxybenzenecarbonitrile In tetrahydrofuran; hexane at -5 - 30℃;	96%
Stage #1: dimethylsulfone With n-butyllithium In tetrahydrofuran; hexane at 0 - 5℃; for 1h; Stage #2: 3-ethoxy-4-methoxybenzenecarbonitrile In tetrahydrofuran; hexane at 0 - 30℃; for 2h;	83%
Stage #1: dimethylsulfone With n-butyllithium In tetrahydrofuran; hexane at 0 - 5℃; for 1h; Stage #2: 3-ethoxy-4-methoxybenzenecarbonitrile In tetrahydrofuran; hexane at 0 - 30℃; for 2h;	83%
Stage #1: dimethylsulfone With sodium amide In tetrahydrofuran; dimethyl sulfoxide at 40℃; Stage #2: 3-ethoxy-4-methoxybenzenecarbonitrile In tetrahydrofuran; dimethyl sulfoxide at 20℃; for 3.5h; Reagent/catalyst; Solvent; Temperature;	83%

dimethylsulfone (67-71-0) + 3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3) → 1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethan-1-one (1450657-28-9)

Conditions	Yield
Stage #1: dimethylsulfone With n-butyllithium In tetrahydrofuran; hexane Large scale; Stage #2: 3-ethoxy-4-methoxybenzenecarbonitrile In tetrahydrofuran; hexane at 0 - 5℃; Large scale; Stage #3: With hydrogenchloride; water In tetrahydrofuran; hexane Large scale;	93%
Stage #1: dimethylsulfone With n-butyllithium In tetrahydrofuran; hexane at 0℃; for 1h; Inert atmosphere; Stage #2: 3-ethoxy-4-methoxybenzenecarbonitrile In tetrahydrofuran; hexane at 0 - 20℃; for 13h; Inert atmosphere;	85%
Stage #1: dimethylsulfone With n-butyllithium In tetrahydrofuran; hexane at 0 - 10℃; for 3h; Inert atmosphere; Stage #2: 3-ethoxy-4-methoxybenzenecarbonitrile In tetrahydrofuran at 0 - 20℃; for 6h;	81%
Stage #1: dimethylsulfone With n-butyllithium In tetrahydrofuran; hexane at 0 - 10℃; for 3h; Inert atmosphere; Industrial scale; Stage #2: 3-ethoxy-4-methoxybenzenecarbonitrile In tetrahydrofuran at 0 - 20℃; for 6h; Solvent; Concentration; Industrial scale;	81%

3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3) + dimethyl sulfoxide (67-68-5) → (1S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfinyl)ethylamine

Conditions	Yield
Stage #1: dimethyl sulfoxide With n-butyllithium In tetrahydrofuran; hexane at 0 - 5℃; for 1.5h; Stage #2: 3-ethoxy-4-methoxybenzenecarbonitrile With tri-n-butylstannyl chloride In tetrahydrofuran at 15 - 20℃; for 2.5h;	85.2%
Stage #1: dimethyl sulfoxide With n-butyllithium In tetrahydrofuran; hexane at 0 - 5℃; for 1.5h; Stage #2: 3-ethoxy-4-methoxybenzenecarbonitrile With tributyltin chloride In tetrahydrofuran; hexane; water at 15 - 20℃; for 14.5h; Time;	109.6 g

dimethylsulfone (67-71-0) + 3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3) → 2-(3-ethoxy-4-methoxyphenyl)-1-(methylsulfonyl)eth-2-ylamine (253168-94-4)

Conditions	Yield
Stage #1: dimethylsulfone With n-butyllithium In tetrahydrofuran; hexane at 0 - 5℃; Stage #2: 3-ethoxy-4-methoxybenzenecarbonitrile In tetrahydrofuran; hexane at 0 - 20℃; Product distribution / selectivity; Inert atmosphere;	76.1%
Stage #1: dimethylsulfone With potassium hexamethylsilazane In tetrahydrofuran at 0 - 10℃; for 1h; Large scale; Stage #2: 3-ethoxy-4-methoxybenzenecarbonitrile In tetrahydrofuran for 0.5h; Large scale; Stage #3: With sodium tetrahydroborate; acetic acid In tetrahydrofuran at 0 - 62℃; Temperature; Large scale;	65%
Stage #1: dimethylsulfone With potassium tert-butylate In dimethyl sulfoxide at 30℃; for 3h; Stage #2: 3-ethoxy-4-methoxybenzenecarbonitrile In tetrahydrofuran; dimethyl sulfoxide for 3.5h; Stage #3: With sodium tetrahydroborate In tetrahydrofuran; dimethyl sulfoxide at 30℃; for 1h;	50%
Stage #1: dimethylsulfone With n-butyllithium In tetrahydrofuran at 0 - 5℃; for 1.5h; Stage #2: 3-ethoxy-4-methoxybenzenecarbonitrile In tetrahydrofuran at 0 - 30℃; for 1.5h; Further stages;

3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3) → 3-ethoxy-4-methoxythiobenzamide (60758-99-8)

Conditions	Yield
With pyridine; hydrogen sulfide; triethylamine Ambient temperature;
With hydrogenchloride; thioacetamide In N,N-dimethyl-formamide at 100℃; for 2h;

3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3) → 6-[2-(3-Ethoxy-4-methoxy-phenyl)-thiazol-4-yl]-3,4-dihydro-1H-quinolin-2-one

Conditions	Yield
Multi-step reaction with 2 steps 1: aq. HCl, thioacetamide / dimethylformamide / 2 h / 100 °C 2: ethanol / 2 h / Heating View Scheme

3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3) → 2-(3-ethoxy-4-methoxyphenyl)-4-(2'-pyrazinyl)thiazole (115540-95-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogen sulphide gas, triethylamine, pyridine / Ambient temperature 2: ethanol / Heating View Scheme

3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3) → 2-(3-ethoxy-4-methoxyphenyl)-4-(5'-nitro-2'-furyl)thiazole (115541-17-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogen sulphide gas, triethylamine, pyridine / Ambient temperature 2: ethanol / Heating View Scheme

3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3) → 3-ethoxy-4-methoxybenzylamine (108439-67-4)

Conditions	Yield
In tetrahydrofuran; ethyl acetate

3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3) → 3-(3-ethoxy-4-methoxyphenyl)-5-(piperidin-4-yl)-1,2,4-oxadiazole (1312793-92-2)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: hydroxylamine hydrochloride; sodium carbonate / ethanol; water / 18 h / 0 °C / Reflux 2.1: dicyclohexyl-carbodiimide / N,N-dimethyl-formamide / 1 h / 0 °C / Inert atmosphere 2.2: 3.5 h / 0 - 30 °C / Inert atmosphere 3.1: N,N-dimethyl-formamide / 10 h / 110 °C / Inert atmosphere 4.1: trifluoroacetic acid / dichloromethane / 6 h / 0 - 25 °C View Scheme
Multi-step reaction with 3 steps 1.1: hydroxylamine hydrochloride; sodium hydroxide / ethanol; water / 18 h / 0 °C / Reflux 2.1: dicyclohexyl-carbodiimide / N,N-dimethyl-formamide / 1 h / 0 °C / Inert atmosphere 2.2: 13.5 h / 0 - 110 °C / Inert atmosphere 3.1: trifluoroacetic acid / dichloromethane / 3 h / 25 °C View Scheme

3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3) → C10H14N2O3 (885957-47-1)

Conditions	Yield
With hydroxylamine hydrochloride; sodium carbonate In ethanol; water at 0℃; for 18h; Reflux;
With hydroxylamine hydrochloride; sodium hydroxide In ethanol; water at 0℃; for 18h; Reflux;

3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3) → tert-butyl 4-(3-(3-ethoxy-4-methoxyphenyl)-1,2,4-oxadiazol-5-yl)piperidine-1-carboxylate (1312793-85-3)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: hydroxylamine hydrochloride; sodium carbonate / ethanol; water / 18 h / 0 °C / Reflux 2.1: dicyclohexyl-carbodiimide / N,N-dimethyl-formamide / 1 h / 0 °C / Inert atmosphere 2.2: 3.5 h / 0 - 30 °C / Inert atmosphere 3.1: N,N-dimethyl-formamide / 10 h / 110 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1.1: hydroxylamine hydrochloride; sodium hydroxide / ethanol; water / 18 h / 0 °C / Reflux 2.1: dicyclohexyl-carbodiimide / N,N-dimethyl-formamide / 1 h / 0 °C / Inert atmosphere 2.2: 13.5 h / 0 - 110 °C / Inert atmosphere View Scheme

3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3) → C21H31N3O6

Conditions	Yield
Multi-step reaction with 2 steps 1.1: hydroxylamine hydrochloride; sodium carbonate / ethanol; water / 18 h / 0 °C / Reflux 2.1: dicyclohexyl-carbodiimide / N,N-dimethyl-formamide / 1 h / 0 °C / Inert atmosphere 2.2: 3.5 h / 0 - 30 °C / Inert atmosphere View Scheme

3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3) → (R)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)-ethylamine (608142-27-4)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: n-butyllithium / tetrahydrofuran; hexane / 1 h / 0 - 5 °C 1.2: 2 h / 0 - 30 °C 2.1: bis(1,5-cyclooctadiene)rhodium(I) trifluoromethanesulfonate; hydrogen; (2R)-1-[(1R)-1-[bis(1,1-dimethylethyl)phosphino]ethyl]-2-(diphenylphosphino)ferrocene / 2,2,2-trifluoroethanol / 18 h / 50 °C / 5414.51 Torr / Inert atmosphere View Scheme

3-ethoxy-4-methoxybenzenecarbonitrile (60758-86-3) → (S)-2-[1 (3-ethoxy-4-methoxyphenyl)]-1-methanesulfonyl-2-ethylamine (608141-42-0)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: n-butyllithium / hexane; tetrahydrofuran / Large scale 1.2: 0 - 5 °C / Large scale 1.3: Large scale 2.1: toluene-4-sulfonic acid / toluene / Dean-Stark; Large scale 2.2: Large scale 2.3: Large scale 3.1: hydrogen; 5%-palladium/activated carbon / methanol / 20 °C / Large scale View Scheme
Multi-step reaction with 2 steps 1.1: n-butyllithium / tetrahydrofuran; hexane / 1 h / 0 - 5 °C 1.2: 2 h / 0 - 30 °C 2.1: bis(1,5-cyclooctadiene)rhodium(I) trifluoromethanesulfonate; (2S)-1-[(1S)-1-[bis(1,1-dimethylethyl)phosphino]ethyl]-2-(diphenylphosphino)ferrocene; hydrogen / 2,2,2-trifluoroethanol / 18 h / 50 °C / 13689.1 Torr / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1.1: n-butyllithium / hexane; tetrahydrofuran / 1 h / 0 - 5 °C 1.2: 2 h / 0 - 30 °C 2.1: bis(1,5-cyclooctadiene)rhodium(I) trifluoromethanesulfonate; hydrogen; (R)-(-)-1-[(S)-2-(diphenylphosphino)ferrocenyl]ethyldi-tert-butylphosphine / 2,2,2-trifluoroethanol / 18 h / 50 °C / 4654.46 Torr / Inert atmosphere View Scheme

Upstream product

• 623-11-0 1-methyl-4-nitrosobenzene 
• 98-09-9 benzenesulfonyl chloride 
• 1956-36-1 3-ethoxy-4-methoxybenzaldoxime 
• 247569-94-4 3-methoxy-4-(2-methoxyethoxy)benzoic acid 
• 121-32-4 4-hydroxy-3-ethoxybenzaldehyde 
• 60758-79-4 3-ethoxy-4-hydroxybenzonitrile 
• 74-88-4 methyl iodide 
• 74-96-4 ethyl bromide 
• 52805-46-6 2-methoxy-5-cyanophenol 
• 621-59-0 isovanillin 
• 247570-05-4 3-benzyloxy-4-methoxybenzamide 
• 247569-95-5 3-methoxy-4-(2-methoxyethoxy)benzamide 
• 247569-93-3 4-ethoxy-3-methoxy-benzoic acid amide 
• 247569-89-7 3-ethoxy-4-methoxy-benzoic acid amide 

Downstream Products

• 60758-99-8 3-ethoxy-4-methoxythiobenzamide 
• 108439-67-4 3-ethoxy-4-methoxybenzylamine 
• 608141-42-0 (S)-2-[1 (3-ethoxy-4-methoxyphenyl)]-1-methanesulfonyl-2-ethylamine 
• 1450759-47-3 (1S,1'S)-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonyl]ethyl-N-(1'-phenylethyl)amine hydrochloride 
• 608141-41-9 Apremilast 
• 608141-44-2 R-Apremilast 
• 247568-43-0 2-[1-(tert-butoxycarbonyl)-4-piperidinylamino]-5-nitro-N-(1,3-benzodioxol-5-ylmethyl)benzamide 
• 247566-98-9 2-(1-Benzylpiperidin-4-ylamino)-5-nitro-N-(1,3-benzodioxol-5-ylmethyl)benzamide 
• 247566-97-8 2-[1-(Ethoxycarbonyl)piperidin-4-ylamino]-5-nitro-N-(1,3-benzodioxol-5-ylmethyl)benzamide 
• 247568-42-9 2-(4-carboxycyclohexylamino)-5-nitro-N-(1,3-benzodioxol-5-ylmethyl)benzamide 
• 247568-41-8 2-[4-(methoxycarbonyl)cyclohexylamino]-5-nitro-N-(1,3-benzodioxol-5-ylmethyl)benzamide 
• 247567-04-0 2-[1-(Hydroxymethyl)cyclopentylamino]-5-nitro-N-(1,3-benzodioxol-5-ylmethyl)benzamide 
• 247566-99-0 2-[2-Hydroxy-1,1-bis(hydroxymethyl)ethylamino]-5-nitro-N-(1,3-benzodioxol-5-ylmethyl)benzamide 
• 247567-06-2 2-[1-(1-Hydroxymethyl)pentylamino]-5-nitro-N-(1,3-benzodioxol-5-ylmethyl)benzamide 

Relevant articles and documents

IMPROVED PROCESS FOR THE PREPARATION OF APREMILAST

The present invention relates to an improved process for the preparation of Apremilast of formula (I).

New synthesis process for 3-methoxyl-4-ethoxybenzonitrile

The invention discloses a new synthesis process for 3-methoxyl-4-ethoxybenzonitrile, and relates to the technical field of organic synthesis. The new synthesis process for the 3-methoxyl-4-ethoxybenzonitrile comprises the following steps: taking ethyl vanillin as a raw material, taking N,N-dimethylformamide as a solvent, reacting the raw material and the solvent with potassium carbonate at first to form potassium salt, and reacting the obtained potassium salt with methyl iodide to obtain 3-methoxyl-4-ethoxy-benzaldehyde as an intermediate; adding hydroxylamine hydrochloride in a formic acid solution of the 3-methoxyl-4-ethoxy-benzaldehyde as the intermediate, heating and dehydrating, and carrying out desolventizing and recrystallization to obtain the high-purity 3-methoxyl-4-ethoxybenzonitrile finished product. The ethyl vanillin which is low in cost and is easily obtained as the raw material, aftertreatment operation is simple, and after being recycled, the N,N-dimethylformamide as the solvent can be directly used for other items; the 3-methoxyl-4-ethoxy-benzaldehyde as the intermediate are used for next reaction when not purified, so that purification cost is saved, and yield loss is avoided; and moreover, solid wastes are not produced in the whole process, and the total yield reaches 93.8%.

Preparation method of chiral S/R-3-ethoxy-4-methoxy-alpha[(methylsulfonyl)methyl] benzyl alcohol

The invention relates to a preparation method of chiral S/R-3-ethoxy-4-methoxy-alpha[(methylsulfonyl)methyl] benzyl alcohol. The preparation method comprises the following steps: 3-hydroxy-4-methoxybenzaldehyde is taken as a starting material and reacts with hydroxylammonium hydrochloride to produce 3-hydroxy-4-methoxybenzonitrile; 3-hydroxy-4-methoxybenzonitrile reacts with bromoethane to produce 3-ethoxy-4-methoxybenzonitrile; 3-ethoxy-4-methoxybenzonitrile reacts with dimethyl sulfone under the action of n-butyllithium, a product is hydrolyzed in an aqueous hydrochloric acid solution, and 1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethanone is obtained; finally, S-(-)-alpha,alpha-diphenyl-2-pyrrolidinemethanol or R-(+)-alpha,alpha-diphenyl-2-pyrrolidinemethanol is taken as a chiral catalyst, a borane dimethyl sulfide solution is taken as a reducing agent, carbonyl is reduced, and a product is obtained. The reaction conditions are mild, the product yield is higher, the technology level is increased, the operability is improved, and large-scale industrial production is facilitated.