2364-75-2

Basic information

• Product Name: 2-ETHYL-3-HYDROXY-6-METHYLPYRIDINE
• Synonyms: CHEMBRDG-BB 5170366;EMOXIPINE;EPIGID;2-ETHYL-6-METHYL-3-PYRIDINOL;2-ETHYL-3-HYDROXY-6-METHYLPYRIDINE;2-ethyl-6-methyl-3-hydroxypyridine;2-ethyl-6-methyl-3-oxypyridine;2-ethyl-6-methyl-3-pyridino
• CAS NO: 2364-75-2
• Molecular Formula: C₈H₁₁NO
• Molecular Weight: 137.18
• EINECS: 502-841-3
• Product Categories: pharmacetical;Pyridines;Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Heterocycle-Pyridine series
• Mol File: 2364-75-2.mol

Chemical Properties

• Melting Point: 136-138
• Boiling Point: 280.6 °C at 760 mmHg
• Flash Point: 123.5 °C
• Appearance: /
• Density: 1.053 g/cm³
• Vapor Pressure: 0.0022mmHg at 25°C
• Refractive Index: 1.536
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 10.59±0.10(Predicted)
• CAS DataBase Reference: 2-ETHYL-3-HYDROXY-6-METHYLPYRIDINE(CAS DataBase Reference)
• NIST Chemistry Reference: 2-ETHYL-3-HYDROXY-6-METHYLPYRIDINE(2364-75-2)
• EPA Substance Registry System: 2-ETHYL-3-HYDROXY-6-METHYLPYRIDINE(2364-75-2)

Safety Data

• Hazard Codes: Xi
• RTECS: UU7714800
• Hazardous Substances Data: 2364-75-2(Hazardous Substances Data)

Usage

Chemical Properties

White to Off-White Solid

Uses

Different sources of media describe the Uses of 2364-75-2 differently. You can refer to the following data:
1. An antidepressant agent.
2. An antidepressant

InChI:InChI=1/C8H11NO/c1-3-7-8(10)5-4-6(2)9-7/h4-5,10H,3H2,1-2H3

Synthetic route

5-methyl-2-propionylfuran (10599-69-6) → emoxypine (2364-75-2)

Conditions	Yield
With ammonia; toluene-4-sulfonic acid at 170℃; under 10501.1 Torr; for 5h; Temperature; Pressure; Autoclave;	96.2%
With ethanol; ammonia at 170℃;
Multi-step reaction with 3 steps 1: NH2OH*HCl, NaOH / ethanol; H2O / 0.33 h / Heating 2: Raney Ni alloy, 2 N aq. NaOH / ethanol / 1 h / Ambient temperature 3: 1.) oxygen, tetraphenylporphine, 2.) triphenylphosphine / 1.) CH2Cl2, -70 deg C, irradiation, 2 h, 2.) -70 deg C, 10 min View Scheme

2-ethyl-6-methylpyridin-3-amine (1344663-48-4) → emoxypine (2364-75-2)

Conditions	Yield
With sulfuric acid; sodium nitrite In water at 0℃; Reflux;	90%

1-(5-methyl-2-furyl)propylamine (64271-00-7) → emoxypine (2364-75-2)

Conditions	Yield
With oxygen; 5,15,10,20-tetraphenylporphyrin; triphenylphosphine 1.) CH2Cl2, -70 deg C, irradiation, 2 h, 2.) -70 deg C, 10 min; Yield given. Multistep reaction;

2-methylfuran (534-22-5) → emoxypine (2364-75-2)

Conditions	Yield
Multi-step reaction with 4 steps 1: FeCl3*6H2O / 1,2-dichloro-ethane / 1 h / Heating 2: NH2OH*HCl, NaOH / ethanol; H2O / 0.33 h / Heating 3: Raney Ni alloy, 2 N aq. NaOH / ethanol / 1 h / Ambient temperature 4: 1.) oxygen, tetraphenylporphine, 2.) triphenylphosphine / 1.) CH2Cl2, -70 deg C, irradiation, 2 h, 2.) -70 deg C, 10 min View Scheme
Multi-step reaction with 2 steps 1: water containing phosphoric acid 2: ethanol; ammonia / 170 °C View Scheme

1-(5-methyl-[2]furyl)-propan-1-one oxime (133712-93-3) → emoxypine (2364-75-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: Raney Ni alloy, 2 N aq. NaOH / ethanol / 1 h / Ambient temperature 2: 1.) oxygen, tetraphenylporphine, 2.) triphenylphosphine / 1.) CH2Cl2, -70 deg C, irradiation, 2 h, 2.) -70 deg C, 10 min View Scheme

2-methyl-5-nitropyridine (21203-68-9) → emoxypine (2364-75-2)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: carbamide peroxide; trifluoroacetic anhydride / dichloromethane / 0 - 20 °C 2.1: tetrahydrofuran / -60 °C / Inert atmosphere 2.2: -60 - 20 °C / Inert atmosphere 3.1: iron; acetic acid / 5 h / 110 °C 4.1: sulfuric acid; sodium nitrite / water / 0 °C / Reflux View Scheme

2-ethyl-6-methyl-3-nitropyridine-1-oxide (1344663-51-9) → emoxypine (2364-75-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: iron; acetic acid / 5 h / 110 °C 2: sulfuric acid; sodium nitrite / water / 0 °C / Reflux View Scheme

2-methyl-5-nitropyridine 1-oxide (36625-50-0) → emoxypine (2364-75-2)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: tetrahydrofuran / -60 °C / Inert atmosphere 1.2: -60 - 20 °C / Inert atmosphere 2.1: iron; acetic acid / 5 h / 110 °C 3.1: sulfuric acid; sodium nitrite / water / 0 °C / Reflux View Scheme

1,3-diethyl 2-(5-nitropyridin-2-yl)propanedioate (60891-70-5) → emoxypine (2364-75-2)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: sulfuric acid / Heating 2.1: carbamide peroxide; trifluoroacetic anhydride / dichloromethane / 0 - 20 °C 3.1: tetrahydrofuran / -60 °C / Inert atmosphere 3.2: -60 - 20 °C / Inert atmosphere 4.1: iron; acetic acid / 5 h / 110 °C 5.1: sulfuric acid; sodium nitrite / water / 0 °C / Reflux View Scheme

emoxypine (2364-75-2) + ethyl bromoacetate (105-36-2) → ethyl (2-ethyl-6-methylpyridyl)-3-oxyacetate (125756-87-8)

Conditions	Yield
With potassium carbonate In acetone for 8h; Heating;	87%
With potassium carbonate 1.) acetone, reflux, 2 h, 2.) acetone, reflux, 8 h; Yield given. Multistep reaction;

emoxypine (2364-75-2) + phosphonic acid diethyl ester (762-04-9) → Phosphoric acid diethyl ester 2-ethyl-6-methyl-pyridin-3-yl ester (121244-60-8)

Conditions	Yield
With triethylamine In tetrachloromethane for 2h; Ambient temperature;	81%

diazomethane (186581-53-3, 908094-01-9) + emoxypine (2364-75-2) → 2-ethyl-3-methoxy-6-methylpyridine

Conditions	Yield
In diethyl ether; ethanol at 0℃;	76%

emoxypine (2364-75-2) → 2-ethyl-6-methylpyridin-3-yl sulfurofluoridate

Conditions	Yield
With fluorosulfonyl fluoride; triethylamine In dichloromethane at 20℃; under 760.051 Torr; for 24h;	71%
Stage #1: emoxypine With triethylamine In acetonitrile at 20℃; for 0.166667h; Stage #2: With 1-(fluorosulfuryl)-2,3-dimethyl-1H-imidazol-3-ium trifluoromethanesulfonate In acetonitrile for 1h;	67%
Stage #1: emoxypine With triethylamine In acetonitrile at 20℃; for 0.166667h; Stage #2: With 1-(fluorosulfuryl)-2,3-dimethyl-1H-imidazol-3-ium trifluoromethanesulfonate In acetonitrile for 1h; Inert atmosphere;	67%

emoxypine (2364-75-2) + bromoacetic acid methyl ester (96-32-2) → methyl 2-((2-ethyl-6-methylpyridin-3-yl)oxy)acetate (1572184-96-3)

Conditions	Yield
With caesium carbonate In acetonitrile at 100℃; for 5h;	70%

emoxypine (2364-75-2) + chloroacetonitrile (107-14-2) → (2-Ethyl-6-methyl-pyridin-3-yloxy)-acetonitrile (194714-30-2)

Conditions	Yield
With potassium carbonate In acetone for 5h; Substitution; Heating;	60%
With potassium carbonate 1.) methylethylketone, reflux, 1 h, 2.) methylethylketone, reflux, 6 h; Yield given. Multistep reaction;

emoxypine (2364-75-2) + chloroacetonitrile (107-14-2) → (2-Ethyl-6-methyl-pyridin-3-yloxy)-acetonitrile (194714-30-2)

Conditions	Yield
With potassium carbonate In acetone for 5h; Substitution; Heating;	60%
With potassium carbonate 1.) methylethylketone, reflux, 1 h, 2.) methylethylketone, reflux, 6 h; Yield given. Multistep reaction;

emoxypine (2364-75-2) + bis(2-ethyl-3-hydroxy-6-methylpyridinium) succinate-succinic acid → bis(2-ethyl-3-hydroxy-6-methylpyridinium) succinate

Conditions	Yield
at 114.84℃; for 0.25h;	59%

emoxypine (2364-75-2) + succinic acid (110-15-6) → bis(2-ethyl-3-hydroxy-6-methylpyridinium)succinate-succinic acid (128228-60-4)

Conditions	Yield
In isopropyl alcohol for 1h; Reflux;	44%

emoxypine (2364-75-2) + 2-bromopropionitrile (19481-82-4) → 2-(2-ethyl-6-methyl-pyridin-3-yloxy)-propionitrile

Conditions	Yield
With potassium carbonate In acetone for 5h; Substitution; Heating;	36%

morpholine (110-91-8) + emoxypine (2364-75-2) + formaldehyd (50-00-0) → 2-ethyl-6-methyl-4-morpholin-4-ylmethyl-pyridin-3-ol

Conditions	Yield
In ethanol

emoxypine (2364-75-2) + epichlorohydrin (106-89-8) → 2-Ethyl-6-methyl-3-oxiranylmethoxy-pyridine

Conditions	Yield
With sodium hydroxide In water at 35 - 45℃; for 5h;

emoxypine (2364-75-2) + ethyl ester of 1-cyclopropyl-6-nitro-4-oxo-7-chloro-1,4-dihydroquinoline-3-carboxylic acid (127625-17-6) → 1-cyclopropyl-7-(2-ethyl-6-methyl-pyridin-3-yloxy)-6-nitro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid ethyl ester

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide at 90℃; for 3h; Substitution; etherification;

emoxypine (2364-75-2) → 2-(6-methyl-2-ethyl-3-pyridyloxymethyl)2-imidazoline

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 60 percent / K2CO3 / acetone / 5 h / Heating 2.1: HCl / diethyl ether / 0 °C 2.2: 21.1 percent / ethanol / 6 h / Heating View Scheme

emoxypine (2364-75-2) → 2-[1-(6-methyl-2-ethyl-3-pyridyloxy)ethyl]imidazoline

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 36 percent / K2CO3 / acetone / 5 h / Heating 2.1: HCl / diethyl ether / 0 °C 2.2: 42 percent / ethanol / 6 h / Heating View Scheme

emoxypine (2364-75-2) → N-(6-methyl-2-ethyl-3-pyridyloxyacetyl)glycineamide

Conditions	Yield
Multi-step reaction with 3 steps 1.1: 60 percent / K2CO3 / acetone / 5 h / Heating 2.1: HCl / diethyl ether / 0 °C 2.2: 21.1 percent / ethanol / 6 h / Heating 3.1: 80 percent / NH3 / methanol / 6 h / 20 °C View Scheme

emoxypine (2364-75-2) → 2-((2-ethyl-6-methylpyridin-3-yl)oxy)acetic acid (132401-72-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) K2CO3 / 1.) acetone, reflux, 2 h, 2.) acetone, reflux, 8 h 2: NaOH / ethanol; H2O / 4 h / Heating View Scheme
Multi-step reaction with 2 steps 1: 87 percent / potash / acetone / 8 h / Heating 2: aq. NaOH / ethanol / 2 h / Heating View Scheme
Multi-step reaction with 2 steps 1.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere 1.2: 20 °C / Inert atmosphere 2.1: trifluoroacetic acid / dichloromethane / 2.5 h / 0 - 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C 1.2: 20 °C 2.1: trifluoroacetic acid / dichloromethane / 2.5 h / 0 - 20 °C View Scheme

emoxypine (2364-75-2) → 2-ethyl-6-methylpyride-3-iloxyacetic amide (132401-87-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) K2CO3 / 1.) acetone, reflux, 2 h, 2.) acetone, reflux, 8 h 2: 6.5 g / NH3, H2O / methanol / 36 h / 20 °C View Scheme

emoxypine (2364-75-2) → 2-ethyl-6-methylpyride-3-iloxyacetic amidoxime (132401-88-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) K2CO3 / 1.) methylethylketone, reflux, 1 h, 2.) methylethylketone, reflux, 6 h 2: NH2OH*HCl, EtONa / ethanol View Scheme

emoxypine (2364-75-2) → O-acetylamidoxime(2-ethyl-6-methylpyride-3-iloxy)acetate (132401-90-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) K2CO3 / 1.) methylethylketone, reflux, 1 h, 2.) methylethylketone, reflux, 6 h 2: NH2OH*HCl, EtONa / ethanol 3: 79.3 percent / dioxane / 16 h / 20 °C View Scheme

emoxypine (2364-75-2) → 2-dimethylaminoethylamide-2-ethyl-6-methylpyride-3-iloxyacetate (132401-66-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) K2CO3 / 1.) acetone, reflux, 2 h, 2.) acetone, reflux, 8 h 2: ethanol / 6 h / Heating View Scheme

emoxypine (2364-75-2) → 2-dimethylaminoethyl 2-ethyl-6-methylpyride-3-iloxyacetate (132401-65-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) K2CO3 / 1.) acetone, reflux, 2 h, 2.) acetone, reflux, 8 h 2: Na / toluene / 4 h / Heating View Scheme

emoxypine (2364-75-2) → N-(3-Dimethylamino-propyl)-2-(2-ethyl-6-methyl-pyridin-3-yloxy)-acetamide (132401-68-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) K2CO3 / 1.) acetone, reflux, 2 h, 2.) acetone, reflux, 8 h 2: ethanol / 6 h / Heating View Scheme

emoxypine (2364-75-2) → 3-dimethylaminopropyl 2-ethyl-6-methylpyride-3-iloxyacetate (132401-69-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) K2CO3 / 1.) acetone, reflux, 2 h, 2.) acetone, reflux, 8 h 2: Na / toluene / 4 h / Heating View Scheme

emoxypine (2364-75-2) → 2-diethylaminoethylamide 2-ethyl-6-methylpyride-3-iloxyacetate (132401-67-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) K2CO3 / 1.) acetone, reflux, 2 h, 2.) acetone, reflux, 8 h 2: methanol / 3 h / Heating View Scheme

Upstream product

• 10599-69-6 5-methyl-2-propionylfuran 
• 64271-00-7 1-(5-methyl-2-furyl)propylamine 
• 534-22-5 2-methylfuran 
• 133712-93-3 1-(5-methyl-[2]furyl)-propan-1-one oxime 
• 21203-68-9 2-methyl-5-nitropyridine 
• 1344663-48-4 2-ethyl-6-methylpyridin-3-amine 
• 1344663-51-9 2-ethyl-6-methyl-3-nitropyridine-1-oxide 
• 36625-50-0 2-methyl-5-nitropyridine 1-oxide 
• 60891-70-5 1,3-diethyl 2-(5-nitropyridin-2-yl)propanedioate 

Downstream Products

• 132401-68-4 N-(3-Dimethylamino-propyl)-2-(2-ethyl-6-methyl-pyridin-3-yloxy)-acetamide 
• 1355026-44-6 C₁₆H₁₇Cl₂NO₂ 
• 128228-60-4 mexidol 

Relevant articles and documents

Improved synthesis method of 6-methyl-2-ethyl-3-hydroxypyridine

The invention discloses an improved synthesis method of 6-methyl-2-ethyl-3-hydroxypyridine, and belongs to the technical field of synthesis of medical intermediates. The method comprises the following steps: 1) reacting propionic anhydride with 2-methyl furan in the presence of a catalyst, washing with water after the reaction is finished, and performing reduced pressure distillation to obtain 5-methyl2-propionyl furan; and 2) mixing the 5-methyl-2-propionyl furan, ammonia water and p-toluenesulfonic acid, carrying out heating reaction, acidifying to be neutral, filtering to obtain a 6-methyl-2-ethyl-3-hydroxypyridine crude product, and recrystallizing to obtain a 6-methyl-2-ethyl-3-hydroxypyridine refined product. The raw materials are easy to obtain, common Lewis acid is added in the step (1), the reaction time is greatly shortened, the good yield is obtained, the acid aqueous solution obtained through washing in the step 1) is used for the acid adjusting process in the step 2), and the three-waste emission problem is basically solved; and 2) the reaction process is simple, a closed heating and pressurizing method is adopted, the raw materials react thoroughly, the yield is high, and the method is suitable for industrial production.

Facile one-pot direct arylation and alkylation of nitropyridine N -oxides with grignard reagents

Facile arylation and alkylation of nitropyridine N-oxides were developed through the reactions of Grignard reagents with nitropyridine N-oxides. For the same 4-nitropyridine N-oxide, arylation occurred at the 2- (or 6-) position, whereas alkylation occurred at the 3-position in an adjustably site-selective manner. The cooperative action of the two groups was discovered in the reactions of 3-nitropyridine N-oxides. This protocol can find wide applications in building various pyridine compounds as illustrated in total syntheses of Emoxipin and Caerulomycin A and E.