5006-20-2

Basic information

• Product Name: 5-Ethoxy-4-methyloxazole
• Synonyms: OXAZOLE(MEO);4-METHYL-5-ETHOXYOXAZOLE;5-ETHOXY-4-METHYLOXAZOLE;OXAZOLE(MEO),4-METHYL-5-ETHOXY-OXAZOLE;4-METHYL-5-ETHOXYOXAZOLE 97+%;5-Ethoxy-4-methyloxazole ,98%;5-ethoxy-4-Methyl-1,3-oxazole;Oxazole,5-ethoxy-4-Methyl-
• CAS NO: 5006-20-2
• Molecular Formula: C₆H₉NO₂
• Molecular Weight: 127.14
• Product Categories: Oxazole&Isoxazole
• Mol File: 5006-20-2.mol
• Article Data: 14

Chemical Properties

• Boiling Point: 164.5 °C at 760 mmHg
• Flash Point: 53.3 °C
• Appearance: /
• Density: 1.04 g/cm³
• Vapor Pressure: 2.58mmHg at 25°C
• Refractive Index: 1.448
• Storage Temp.: Sealed in dry,Store in freezer, under -20°C
• Solubility: Chloroform, Ethyl Acetate (Slightly), Methanol (Slightly)
• PKA: 1.85±0.14(Predicted)
• CAS DataBase Reference: 5-Ethoxy-4-methyloxazole(CAS DataBase Reference)
• NIST Chemistry Reference: 5-Ethoxy-4-methyloxazole(5006-20-2)
• EPA Substance Registry System: 5-Ethoxy-4-methyloxazole(5006-20-2)

Safety Data

• Statements: 36/37/38
• Safety Statements: 26-36/37/39
• Hazardous Substances Data: 5006-20-2(Hazardous Substances Data)

Usage

Chemical Properties

Colorless to light yellow liquid

Uses

5-Ethoxy-4-methoxazole is used in the synthesis mappicine ketone, an antiviral compound.

InChI:InChI=1/C6H9NO2/c1-3-8-6-5(2)7-4-9-6/h4H,3H2,1-2H3

Synthetic route

4-methyl-5-ethoxy-2-carboxyoxazole (23429-05-2) → 5-ethoxy-4-methyl-oxazole (5006-20-2)

Conditions	Yield
With hydrogenchloride In chloroform at 50℃; pH=2.5;	94.8%
at 90℃; for 1h; Temperature;

4-methyl-5-ethoxy-2-oxazole carboxylate ethyl ester (23429-04-1) → 5-ethoxy-4-methyl-oxazole (5006-20-2)

Conditions	Yield
Stage #1: 4-methyl-5-ethoxy-2-oxazole carboxylate ethyl ester With sodium hydroxide Stage #2: With hydrogenchloride	89.9%
With toluene-4-sulfonic acid; acetic acid In toluene at 90℃; for 3h; Solvent; Temperature; Reagent/catalyst;	93.7 %Chromat.
Stage #1: 4-methyl-5-ethoxy-2-oxazole carboxylate ethyl ester With sodium hydroxide In water Stage #2: With hydrogenchloride In water at 60 - 62℃; pH=2.5;

ethyl N-formyl-2-aminopropanoate (4289-99-0) → 5-ethoxy-4-methyl-oxazole (5006-20-2)

Conditions	Yield
With boron trifluoride diethyl etherate; magnesium oxide In dichloromethane at 120℃; for 8h; Reagent/catalyst; Temperature; Solvent; Sealed tube;	71%
With phosphorus pentoxide; magnesium oxide In chloroform for 20h; Heating;	50%
With phosphorus pentoxide In dichloromethane for 48h; Reflux;	50%

AlaOEt (17344-99-9) → 5-ethoxy-4-methyl-oxazole (5006-20-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.5 h / Reflux 2: phosphorus pentoxide; magnesium oxide / chloroform / 20.5 h / 20 °C / Inert atmosphere; Reflux View Scheme
Multi-step reaction with 2 steps 1: 2 h / 160 °C 2: 48 h / Reflux View Scheme

methylglyoxal diethyl acetal (5774-26-5) → 5-ethoxy-4-methyl-oxazole (5006-20-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1 h / 76 °C / Inert atmosphere 2: 2 h / 150 °C / Inert atmosphere View Scheme

1-bromo-1-ethoxyacetone + formamide (77287-34-4, 77287-35-5, 60100-09-6) → 5-ethoxy-4-methyl-oxazole (5006-20-2)

Conditions	Yield
at 150℃; for 2h; Temperature; Inert atmosphere;	30.5 g

1-chloro-1-ethoxyacetone + formamide (77287-34-4, 77287-35-5, 60100-09-6) → 5-ethoxy-4-methyl-oxazole (5006-20-2)

Conditions	Yield
at 130℃; for 2h; Temperature; Inert atmosphere;	28.5 g

N-ethoxyoxalylalanine ethyl ester (23460-73-3) → 5-ethoxy-4-methyl-oxazole (5006-20-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: triethylamine; trichlorophosphate / toluene / 3 h / 55 - 110 °C 2: water; sodium hydroxide / 5 h / 50 - 55 °C / pH 14 3: 1 h / 90 °C View Scheme
With triethylamine; Triphenylphosphine oxide; trichloromethyl chloroformate In dichloromethane at 0 - 50℃; for 2.5h; Reagent/catalyst; Solvent;	97 %Chromat.

4-methyl-5-ethoxyoxazole butyl carboxylate → 5-ethoxy-4-methyl-oxazole (5006-20-2)

Conditions	Yield
With toluene-4-sulfonic acid; acetic acid In 1,4-dioxane at 90℃; for 2h; Reagent/catalyst; Solvent;	93.7 %Chromat.

hexyl 4-methyl-5-ethoxyoxazolecarboxylate → 5-ethoxy-4-methyl-oxazole (5006-20-2)

Conditions	Yield
With sodium acetate; benzoic acid In acetonitrile at 90℃; for 2h;	40.2 %Chromat.

tert-butyl 4-methyl-5-ethoxyoxazolecarboxylic acid → 5-ethoxy-4-methyl-oxazole (5006-20-2)

Conditions	Yield
With sodium acetate; benzoic acid In acetonitrile at 90℃; for 2h;	10.2 %Chromat.

4-methyl-5-ethoxyoxazolecarboxylic acid methyl ester → 5-ethoxy-4-methyl-oxazole (5006-20-2) + ethyl N-formyl-2-aminopropanoate (4289-99-0)

Conditions	Yield
With propionic acid; trifluoroacetic acid In acetonitrile at 70℃; for 3.5h;	A 85.3 %Chromat. B 7 %Chromat.

sodium 4-methyl-5-ethoxy-2-oxazole carboxylate → 5-ethoxy-4-methyl-oxazole (5006-20-2)

Conditions	Yield
With hydrogenchloride In ethanol at 60 - 65℃; for 0.166667h; Temperature; Flow reactor;

N-ethoxyoxalyl-α-alanine ethyl ester → 5-ethoxy-4-methyl-oxazole (5006-20-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: bis(trichloromethyl) carbonate; Triphenylphosphine oxide; triethylamine / toluene / 3 h / 25 - 50 °C 2.1: sodium hydroxide / water 2.2: 60 - 62 °C / pH 2.5 View Scheme

5-ethoxy-4-methyl-oxazole (5006-20-2) + 2-isopropyl-4,7-dihydro-[1,3]dioxepine (5417-35-6) + acetic anhydride (108-24-7) → 8-methyl-3-(propan-2-yl)-1H,3H,5H-[1,3]dioxepino[5,6-c]pyridin-9-yl acetate (92671-67-5)

Conditions	Yield
at 140 - 145℃; under 1500.15 - 2250.23 Torr; for 8h; Temperature; Pressure; Autoclave; Inert atmosphere;	97.7%

5-ethoxy-4-methyl-oxazole (5006-20-2) + acetic anhydride (108-24-7) + 2-propyl-4,7-dihydro-2H-1,3-dioxepine (4469-34-5) → 8-methyl-3-propyl-1H,3H,5H-[1,3]dioxepino[5,6-c]pyridin-9-yl acetate

Conditions	Yield
at 135 - 145℃; under 1500.15 - 2250.23 Torr; for 8h; Temperature; Pressure; Autoclave; Inert atmosphere;	97.5%

5-ethoxy-4-methyl-oxazole (5006-20-2) + 2-propyl-4,7-dihydro-2H-1,3-dioxepine (4469-34-5) → C14H23NO4

Conditions	Yield
With titanium(IV) oxide at 100℃; for 8h; Time; Reagent/catalyst; Temperature; Diels-Alder Cycloaddition; Inert atmosphere; Irradiation;	96.2%
With sodium-type cation exchange resin In cyclohexane at 80 - 150℃; for 15h; Temperature; Diels-Alder Cycloaddition;

5-ethoxy-4-methyl-oxazole (5006-20-2) + ethyl acrylate (140-88-5) → 3-methyl-4-ethoxy-5-ethoxycarbonyl-7-oxa-2-azabicyclo<2,2,1>-2-heptene

Conditions	Yield
at 40℃; for 4h;	93%

5-ethoxy-4-methyl-oxazole (5006-20-2) + phenylpropynoic acid ethyl ester (2216-94-6) → 4-phenyl-3-carbethoxy-2-ethoxy furan

Conditions	Yield
In toluene for 3h; Heating;	90%

5-ethoxy-4-methyl-oxazole (5006-20-2) + acrylonitrile (107-13-1) → 2-methyl-3-hydroxy-4-cyanopyridine (13602-91-0)

Conditions	Yield
for 4h; Ambient temperature;	85%

5-ethoxy-4-methyl-oxazole (5006-20-2) + acrylic acid (79-10-7) → 2-methyl-3-hydroxy-4-pyridinecarboxylic acid (4328-92-1)

Conditions	Yield
Ambient temperature;	85%
at 4℃; Diels-Alder reaction;	60%
at 4 - 20℃;

5-ethoxy-4-methyl-oxazole (5006-20-2) + 2-formyl-4,4-dimethylcyclohexa-2,5-dien-1-one (30758-46-4) → 1-ethoxycarbonyl-4,7-dihydro-7-oxo-1,4,4-trimethyl-(1H)-isoindole

Conditions	Yield
With zinc dibromide In benzene for 0.5h; Heating;	85%

5-ethoxy-4-methyl-oxazole (5006-20-2) + 2-propyl-4,7-dihydro-2H-1,3-dioxepine (4469-34-5) → pyridoxal hydrochloride (58-56-0)

Conditions	Yield
With hydrogenchloride Diels-Alder Cycloaddition;	78.5%

5-ethoxy-4-methyl-oxazole (5006-20-2) + methyl 5-methylhex-5-en-2-yonate → 2-Ethoxy-4-(2-methyl-allyl)-furan-3-carboxylic acid methyl ester

Conditions	Yield
In toluene at 120℃; for 24h;	65%

5-ethoxy-4-methyl-oxazole (5006-20-2) + 1-ethyl-3-formyl-2-propynyl benzoate (229176-13-0) → 5-ethoxy-4-formyl-3-(1-phenylcarbonyloxypropyl)furan (229176-14-1)

Conditions	Yield
In toluene for 12h; Diels-Alder reaction; Heating;	65%

2,5-dihydrofuran (1708-29-8) + 5-ethoxy-4-methyl-oxazole (5006-20-2) → 7-hydroxy-6-methyl-1,3-dihydrofuro<3,4-c>pyridin (5196-20-3)

Conditions	Yield
With trichloroacetic acid at 200℃; for 5h; Diels-Alder Cycloaddition;	57%

5-ethoxy-4-methyl-oxazole (5006-20-2) + trifluoromethyacrylic acid (381-98-6) → 2-methyl 4-trifluoromethyl pyridin-3-ol

Conditions	Yield
In toluene at 120℃; for 48h;	56%

5-ethoxy-4-methyl-oxazole (5006-20-2) + ethyl <3-oxo-2H-isothiazol-2-yl>acetate 1,1-dioxide (126623-60-7) → Ethyl 4α-Ethoxy-2,3,3aα,4,7α,7aα-hexahydro-5-methyl-3-oxo-4,7-epoxyisothiazolo<5,4-c>pyridine-2-acetate 1,1-Dioxide (127872-24-6)

Conditions	Yield
In benzene Ambient temperature;	55%

5-ethoxy-4-methyl-oxazole (5006-20-2) + 3-(3-bromo-4-methoxyphenyl)-1-phenylprop-2-yn-1-one → 3-benzoyl-4-(3-bromo-4-methoxyphenyl)furan-2(5H)-one

Conditions	Yield
Stage #1: 5-ethoxy-4-methyl-oxazole; 3-(3-bromo-4-methoxyphenyl)-1-phenylprop-2-yn-1-one In 5,5-dimethyl-1,3-cyclohexadiene at 145 - 150℃; for 24h; Inert atmosphere; Stage #2: With hydrogen bromide In tetrahydrofuran; water at 20℃; for 8h; Inert atmosphere;	51%

5-ethoxy-4-methyl-oxazole (5006-20-2) + 5-(4-methoxyphenoxy)pent-3-yn-2-one (174001-36-6) → 3-acetyl-2-ethoxy-4-[(4-methoxyphenoxy)methyl]furan (330623-29-5)

Conditions	Yield
In toluene for 3h; tandem Diels-Alder-retro-Diels-Alder reaction; Heating;	46%

5-ethoxy-4-methyl-oxazole (5006-20-2) + 2-(p-methoxybenzyl)isothiazol-3(2H)-one 1,1-dioxide (126623-61-8) → 4α-Ethoxy-3aα,4,7α,7aα-tetrahydro-2-(4-methoxybenzyl)-5-methyl-4,7-epoxyisothiazolo<5,4-c>pyridin-3(2H)-one 1,1 Dioxide (127872-23-5)

Conditions	Yield
In benzene Ambient temperature;	45%

5-ethoxy-4-methyl-oxazole (5006-20-2) + 2-vinyl pyridine hydrochloride (2479-59-6) → 2'-Methyl-[2,4']bipyridinyl-3'-ol (76162-92-0)

Conditions	Yield
In acetic acid 1.)reflux, 8 h 2.)r.t., overnight;	45%

5-ethoxy-4-methyl-oxazole (5006-20-2) + Diethyl maleate (141-05-9) → (1RS,4SR,5SR,6RS)-4-ethoxy-3-methyl-7-oxa-2-azabicyclo[2.2.1]hept-2-ene-5,6-dicarboxylic acid diethyl ester + (1RS,4SR,5RS,6SR)-4-ethoxy-3-methyl-7-oxa-2-azabicyclo[2.2.1]hept-2-ene-5,6-dicarboxylic acid diethyl ester

Conditions	Yield
at 110℃; for 3h; Diels-Alder reaction;	A 24% B 41%

5-ethoxy-4-methyl-oxazole (5006-20-2) + 4,4-dimethylcyclohexenone (1073-13-8) → 1-ethoxycarbonyl-7-oxo-4,5,6,7-tetrahydro-1,4,4-trimethyl-(1H)-isoindole

Conditions	Yield
With zinc dibromide In benzene for 48h; Heating;	35%

5-ethoxy-4-methyl-oxazole (5006-20-2) + methanol (67-56-1) + 3-chloroacrylic acid (1609-93-4) → 2-methyl-3-hydroxy-4-carboxy-6-methoxypyridine

Conditions	Yield
Ambient temperature;	33%

5-ethoxy-4-methyl-oxazole (5006-20-2) + ethanol (64-17-5) + 3-chloroacrylic acid (1609-93-4) → 2-methyl-3-hydroxy-4-carboxy-6-ethoxypyridine

Conditions	Yield
Ambient temperature;	29%

5-ethoxy-4-methyl-oxazole (5006-20-2) + 3-chloroacrylic acid (1609-93-4) + ethylene glycol (107-21-1) → 2-methyl-3-hydroxy-4-carboxy-6-(2-hydroxyethyloxy)pyridine

Conditions	Yield
Ambient temperature;	25%

5-ethoxy-4-methyl-oxazole (5006-20-2) + 3-chloroacrylic acid (1609-93-4) + thiophenol (108-98-5) → 2-methyl-3-hydroxy-4-carboxy-6-phenylthiopyridine

Conditions	Yield
Ambient temperature;	25%

5-ethoxy-4-methyl-oxazole (5006-20-2) + ethyl 4,4,4-trifluorocrotonate (25597-16-4) → 2-methyl-3-hydroxy-5-trifluoromethylisonicotinic acid ethyl ester + 2-(acetyl)-3-(carboethoxy)-4-trifluoromethyl pyrrole

Conditions	Yield
at 120℃; for 48h;	A 25% B 8%

5-ethoxy-4-methyl-oxazole (5006-20-2) + 3-chloroacrylic acid (1609-93-4) + isopropyl alcohol (67-63-0) → 2-methyl-3-hydroxy-4-carboxy-6-(2-propyloxy)pyridine

Conditions	Yield
Ambient temperature;	24%

5-ethoxy-4-methyl-oxazole (5006-20-2) + 3,4-dimethyl-cyclohex-2-enone (10463-42-0) → 1,4-Dimethyl-7-oxo-3a,4,5,6,7,7a-hexahydro-1H-isoindole-1-carboxylic acid ethyl ester

Conditions	Yield
With zinc dibromide In benzene at 90℃; for 12h;	24%

Upstream product

• 20902-48-1 N-ethoxyoxalyl-α-alanine ethyl ester 
• 23429-05-2 4-methyl-5-ethoxy-2-carboxyoxazole 
• 23460-73-3 N-ethoxyoxalylalanine ethyl ester 
• 77287-34-4 formamide 
• 5774-26-5 methylglyoxal diethyl acetal 
• 23429-04-1 4-methyl-5-ethoxy-2-oxazole carboxylate ethyl ester 
• 17344-99-9 AlaOEt 
• 4289-99-0 ethyl N-formyl-2-aminopropanoate 

Downstream Products

• 229176-14-1 5-ethoxy-4-formyl-3-(1-phenylcarbonyloxypropyl)furan 
• 330623-29-5 3-acetyl-2-ethoxy-4-[(4-methoxyphenoxy)methyl]furan 
• 846055-93-4 3-hydroxy-2-methyl-5-trifluoromethylisonicotinonitrile 
• 58-56-0 pyridoxal hydrochloride 
• 92671-67-5 8-methyl-3-(propan-2-yl)-1H,3H,5H-[1,3]dioxepino[5,6-c]pyridin-9-yl acetate 
• 5196-20-3 7-hydroxy-6-methyl-1,3-dihydrofuro<3,4-c>pyridin 
• 5205-63-0 Diels-Alder adduct 
• 33140-27-1 ethyl 2-isocyanopropionate 
• 1622-67-9 4,5'-O-isobutylidenepyridoxine 
• 208777-63-3 2-Ethoxyfuran-3-carboxylic acid 
• 156969-65-2 Benzoic acid 1-benzyloxycarbonyl-1-(5-ethoxy-4-formyl-furan-3-yl)-propyl ester 
• 127872-23-5 4α-Ethoxy-3aα,4,7α,7aα-tetrahydro-2-(4-methoxybenzyl)-5-methyl-4,7-epoxyisothiazolo<5,4-c>pyridin-3(2H)-one 1,1 Dioxide 

Relevant articles and documents

Evaluation of 2-methyl-3-hydroxy-4-pyridinecarboxylic acid as a possible chelating agent for iron and aluminium

In view of a possible application to Fe and Al chelation therapy, 2-methyl-3-hydroxy-4-pyridinecarboxylic acid (DT2) was synthesised, and its complex formation, electrochemical and cytotoxic properties were studied. The complexing properties of DT2 towards Fe(iii) and Al(iii) were investigated in aqueous 0.6 m (Na)Cl at 25 °C by means of potentiometric titrations, UV-vis spectrophotometry, and 1H NMR spectroscopy. DT2 is a triprotic acid (H3L+) having pKa1 = 0.47, pKa2 = 5.64 and pKa3 = 11.18. The metal-ligand complexes observed in solution and their corresponding stability constants (logβ values) are the following: FeLH (19.38), FeL (16.01), FeLH-1 (12.28), FeL 2H2 (37.29), FeL3H3 (53.41), FeL3H2 (47.99), FeL3H (41.21) and FeL 3 (34.1); AlLH (17.43), AlL2H2 (33.74), AlL2H (27.6), AlL3H3 (48.72), AlL 3H2 (42.67), AlL3H (35.8) and AlL3 (27.92). The complex formation between DT2 and Fe(ii) was studied by UV-vis: the weak complex FeLH (logβ = 15.8) was detected. DT2 shows a lower complexation efficiency with Fe(iii) and Al(iii) than that of other available chelators, but higher than that of its non-methylated analogue 3-hydroxy-4-pyridinecarboxylic acid (DT0). The electrochemical behaviour of DT2 was investigated by means of cyclic voltammetry, indicating that the oxidation of the ligand proceeds through a two electron process with a CECE mechanism. Voltammetric curves suggest that the oxidation or the reduction of DT2 in vivo is unlikely. According to the thermodynamic data, also the Fe(iii)-DT2 complexes do not undergo redox cycling at physiological pH. Amperometric titrations of solutions containing Fe(iii) and DT2 at pH = 5 indicated the same Fe(iii): ligand stoichiometric ratio as calculated from potentiometric data. The toxicity of DT2 and of other simple hydroxypyridinecarboxylic acids was investigated in vitro and no cytotoxic activity was observed (IC50 > 0.1 mM) on cancer cell lines and also on primary human cells, following a three day exposure. The Royal Society of Chemistry.

Preparation method of 4-methyl-5-ethoxy oxazole

The invention discloses a preparation method of 4-methyl-5-ethoxy oxazole, which comprises the following steps of by using N-formyl alanine ethyl ester as a raw material, directly cyclizing in the presence of boron trifluoride diethyl etherate and metal oxide to obtain 4-methyl-5-ethoxy oxazole, which has a reaction general formula (1). The preparation method of the novel 4-methyl-5-ethoxy oxazole is short in route, simple to operate, high in conversion rate and good in atom economy, the used materials such as boron trifluoride diethyl ether can be recycled and reused, a large amount of wastewater cannot be generated, and the preparation method is very suitable for industrial production.

Preparation method of 4-alkyl-5-alkoxy oxazole compound

The invention discloses a preparation method of a 4-alkyl-5-alkoxy oxazole compound. The preparation method comprises the following steps: under the action of a catalyst, carrying out transesterification on 4-alkyl-5-alkoxy oxazole-2-carboxylic ester and acid in a solvent to obtain an oxazole acid intermediate, and carrying out decarboxylation reaction on the oxazole acid intermediate to obtain the 4-alkyl-5-alkoxy oxazole compound. The preparation method has the advantages of no wastewater generation in the reaction process, cheap and accessible catalyst and high reaction yield, and is convenient for industrial production.