693-93-6

Basic information

• Product Name: 4-methyloxazole
• Synonyms: 4-methyloxazole;Oxazole, 4-methyl-;Einecs 211-763-6;4-Methyl-1,3-oxazole;4-Methyloxazole HCl
• CAS NO: 693-93-6
• Molecular Formula: C₄H₅NO
• Molecular Weight: 83.0886
• EINECS: 211-763-6
• Mol File: 693-93-6.mol
• Article Data: 2

Chemical Properties

• Boiling Point: 88℃
• Flash Point: 21℃
• Appearance: /
• Density: 1.016
• Vapor Pressure: 70.1mmHg at 25°C
• Refractive Index: 1.4317
• Storage Temp.: 2-8°C
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 1.33±0.14(Predicted)
• CAS DataBase Reference: 4-methyloxazole(CAS DataBase Reference)
• NIST Chemistry Reference: 4-methyloxazole(693-93-6)
• EPA Substance Registry System: 4-methyloxazole(693-93-6)

Safety Data

• RIDADR: 1993
• HazardClass: 3
• PackingGroup: Ⅱ
• Hazardous Substances Data: 693-93-6(Hazardous Substances Data)

Usage

Uses

4-Methyloxazole is used in the synthesis of quinuclidine-based ligands as muscarinic cholinergic receptor agonists. Also used in the synthesis of oxazoles and oxazolines.

InChI:InChI=1/C4H5NO/c1-4-2-6-3-5-4/h2-3H,1H3

Synthetic route

4-methyl-1,3-oxazole-5-carboxylic acid (2510-32-9) → 4-methyloxazole (693-93-6)

Conditions	Yield
With copper(II) oxide at 180℃;	75%
With copper(II) oxide

rac-octan-2-ol (4128-31-8) + hydroxy-2-propanone (116-09-6) → 4-methyloxazole (693-93-6)

Conditions	Yield
With hydrogenchloride; sodium hydroxide; hydrogen isocyanide In N,N-dimethyl-aniline; 1,2-dichloro-benzene

hydroxy-2-propanone (116-09-6) → 4-methyloxazole (693-93-6)

Conditions	Yield
With N,N-diethylaniline
With hydrogenchloride; hydrogen isocyanide In N,N-dimethyl-aniline; nitrobenzene; cyclohexanol

2-Methylcyclohexanol (583-59-5) + hydroxy-2-propanone (116-09-6) → 4-methyloxazole (693-93-6)

Conditions	Yield
With hydrogenchloride; hydrogen isocyanide In dichloromethane; N,N-dimethyl-aniline

formimido-cyclohexyl ester hydrochloride + hydroxy-2-propanone (116-09-6) → 4-methyloxazole (693-93-6)

Conditions	Yield
With N,N-diethylaniline
With 1-methyl-pyrrolidin-2-one; N,N-diethylaniline

formimido-cyclohexyl ester + hydroxy-2-propanone (116-09-6) → 4-methyloxazole (693-93-6)

4-methyloxazole (693-93-6) + 4-methylphenyl methylsulfide (623-13-2) → 4-methyl-2-(p-tolyl)oxazole (83081-31-6)

Conditions	Yield
With [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl) palladium(II) dichloride; 2,2,6,6-tetramethylpiperidyl zinc chloride-lithium chloride complex In tetrahydrofuran at 80℃; for 6h; Inert atmosphere; regioselective reaction;	98%

4-methyloxazole (693-93-6) + triisopropylsilyl trifluoromethanesulfonate (80522-42-5) → 4-methyl-2-(triisopropylsilyl)oxazole

Conditions	Yield
Stage #1: 4-methyloxazole With n-butyllithium In tetrahydrofuran; hexane at -30℃; for 0.5h; Stage #2: triisopropylsilyl trifluoromethanesulfonate In tetrahydrofuran; hexane at -10℃;	98%
Stage #1: 4-methyloxazole With n-butyllithium In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: triisopropylsilyl trifluoromethanesulfonate In tetrahydrofuran at -10 - 25℃; for 12h; Inert atmosphere;	81%

4-methyloxazole (693-93-6) + C14H15BrN6O4 → C18H19N7O5 (1340588-62-6)

Conditions	Yield
Stage #1: 4-methyloxazole With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.166667h; Stage #2: With zinc(II) chloride In tetrahydrofuran; hexane at -78℃; for 0.25h; Stage #3: C14H15BrN6O4 With bis-triphenylphosphine-palladium(II) chloride In tetrahydrofuran; hexane at 75℃; for 0.166667h; Negishi coupling reaction; Inert atmosphere; Microwave irradiation;	88%

4-methyloxazole (693-93-6) + 3-<1-(Methoxycarbonyl)cyclopropyl>-2-propinsaeure-methylester (104462-87-5) → 4-<1-(Methoxycarbonyl)cyclopropyl>-3-furancarbonsaeure-methylester (104462-98-8)

Conditions	Yield
at 220℃; for 20h;	87%

4-methyloxazole (693-93-6) + chloro-trimethyl-silane (75-77-4) → (Z)-2-isocyano-O-(trimethylsilyl)-1-propen-1-ol (90892-92-5)

Conditions	Yield
With n-butyllithium In diethyl ether at -78℃;	85%
With n-butyllithium 1.) hexane, Et2O, 1 h; Yield given. Multistep reaction;

4-methyloxazole (693-93-6) + (2-amino-6-bromo-3-nitropyridin-4-yl)-(6-methylpyridin-3-ylmethyl)carbamic acid ethyl ester (947145-09-7) → [2-amino-6-(4-methyloxazol-2-yl)-3-nitropyridin-4-yl]-(6-methylpyridin-3-ylmethyl)carbamic acid ethyl ester (947143-92-2)

Conditions	Yield
Stage #1: 4-methyloxazole With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.166667h; Stage #2: With zinc(II) chloride In tetrahydrofuran; hexane at -78℃; for 0.25h; Stage #3: (2-amino-6-bromo-3-nitropyridin-4-yl)-(6-methylpyridin-3-ylmethyl)carbamic acid ethyl ester With bis-triphenylphosphine-palladium(II) chloride In tetrahydrofuran; hexane at 60℃; for 0.25h; Negishi coupling reaction; Inert atmosphere; Microwave irradiation;	85%
Stage #1: 4-methyloxazole With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.166667h; Cooling with acetone-dry ice; Stage #2: With zinc(II) chloride In tetrahydrofuran; hexane at -78 - 20℃; for 0.25h; Stage #3: (2-amino-6-bromo-3-nitropyridin-4-yl)-(6-methylpyridin-3-ylmethyl)carbamic acid ethyl ester; bis-triphenylphosphine-palladium(II) chloride In tetrahydrofuran; hexane at 60℃; for 0.25h; Microwave irradiation;

4-methyloxazole (693-93-6) + methyl 3-<1'-chlorocyclopropyl>propiolate (83662-44-6) → 4-(1-Chlorcyclopropyl)-3-furancarbonsaeure-methylester (104462-97-7) + acetonitrile (75-05-8)

Conditions	Yield
at 140℃;	A 80% B n/a

4-methyloxazole (693-93-6) + acetyl chloride (75-36-5) → (Z)-2-isocyano-O-acetyl-1-propen-1-ol (90892-91-4)

Conditions	Yield
With n-butyllithium In diethyl ether at -78℃;	80%
With n-butyllithium 1.) hexane, Et2O, 1 h; Yield given. Multistep reaction;

4-methyloxazole (693-93-6) + C15H16BrN5O5 → C19H20N6O6 (1340588-61-5)

Conditions	Yield
Stage #1: 4-methyloxazole With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.166667h; Stage #2: With zinc(II) chloride In tetrahydrofuran; hexane at -78℃; for 0.25h; Stage #3: C15H16BrN5O5 With bis-triphenylphosphine-palladium(II) chloride In tetrahydrofuran; hexane at 90℃; for 0.0833333h; Negishi coupling reaction; Inert atmosphere; Microwave irradiation;	80%

4-methyloxazole (693-93-6) + C14H15BrN6O4 → C18H19N7O5 (1340588-60-4)

Conditions	Yield
Stage #1: 4-methyloxazole With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.166667h; Stage #2: With zinc(II) chloride In tetrahydrofuran; hexane at -78℃; for 0.25h; Stage #3: C14H15BrN6O4 With bis-triphenylphosphine-palladium(II) chloride In tetrahydrofuran; hexane at 65℃; for 1h; Negishi coupling reaction; Inert atmosphere;	75%

4-methyloxazole (693-93-6) + 4-bromo-2-methylpyridine (22282-99-1) → 4-methyl-2-(2-methylpyridin-4-yl)oxazole

Conditions	Yield
Stage #1: 4-methyloxazole With n-butyllithium; zinc(II) chloride In tetrahydrofuran; 2-methyltetrahydrofuran at -78 - 22℃; for 0.5h; Stage #2: 4-bromo-2-methylpyridine With tetrakis(triphenylphosphine) palladium(0) In tetrahydrofuran; 2-methyltetrahydrofuran at 60℃; for 2h;	70%

4-methyloxazole (693-93-6) + 3,3,3-trifluoroprop-1-yne (661-54-1) → 3-trifluoromethyl furan (56286-84-1) + acetonitrile (75-05-8)

Conditions	Yield
In toluene at 180 - 190℃; for 13h;	A 67% B 6%

4-methyloxazole (693-93-6) + (2-amino-6-bromo-3-nitro-pyridin-4-yl)-(3-cyano-benzyl)-carbamic acid ethyl ester (947145-74-6) → [2-amino-6-(4-methyl-oxazol-2-yl)-3-nitro-pyridin-4-yl]-(3-cyano-benzyl)-carbamic acid ethyl ester (947145-82-6)

Conditions

Yield

Stage #1: 4-methyloxazole With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.166667h; Stage #2: With zinc(II) chloride In tetrahydrofuran; hexane at -78℃; for 0.25h; Stage #3: (2-amino-6-bromo-3-nitro-pyridin-4-yl)-(3-cyano-benzyl)-carbamic acid ethyl ester With bis-triphenylphosphine-palladium(II) chloride In tetrahydrofuran; hexane at 60℃; for 0.25h; Negishi coupling reaction; Inert atmosphere; Microwave irradiation;

65%

4-methyloxazole (693-93-6) + tributyltin chloride (1461-22-9) → 4-methyl-2-(tributylstannyl)oxazole

Conditions	Yield
Stage #1: 4-methyloxazole With n-butyllithium In tetrahydrofuran; diethyl ether at -78℃; for 1h; Stage #2: tributyltin chloride In tetrahydrofuran; diethyl ether at -78℃; for 1h;	61%
Stage #1: 4-methyloxazole In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: tributyltin chloride In tetrahydrofuran at 20℃; for 1h; Inert atmosphere;

4-methyloxazole (693-93-6) → 2-bromo-4-methyloxazole

Conditions	Yield
Stage #1: 4-methyloxazole With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.666667h; Stage #2: With 1,2-dibromo-1,1,2,2-tetrafluoroethane In tetrahydrofuran; hexane at -78 - 25℃; regioselective reaction;	61%

4-methyloxazole (693-93-6) + 5-bromo-2-methylpyridine (3430-13-5) → 4-methyl-2-(6-methylpyridin-3-yl)oxazole

Conditions	Yield
Stage #1: 4-methyloxazole With n-butyllithium; zinc(II) chloride In tetrahydrofuran; 2-methyltetrahydrofuran at -78 - 22℃; for 0.5h; Stage #2: 5-bromo-2-methylpyridine With tetrakis(triphenylphosphine) palladium(0) In tetrahydrofuran; 2-methyltetrahydrofuran at 60℃; for 2h;	53%

4-methyloxazole (693-93-6) + 5-bromo-2-(cyanomethyl)benzonitrile (925672-89-5) → 2-(cyanomethyl)-5-(4-methyl-1,3-oxazol-5-yl)benzonitrile

Conditions	Yield
With potassium acetate; palladium diacetate In N,N-dimethyl-formamide at 90℃; for 3h; Inert atmosphere;	50%

4-methyloxazole (693-93-6) + 3-Cyclopropyl-2-propinsaeure-methylester (80866-48-4) → 4-Cyclopropyl-3-furancarbonsaeure-methylester (104462-89-7)

Conditions	Yield
In toluene at 220 - 230℃; for 16h;	45%

4-methyloxazole (693-93-6) + methyl 2-bromoisonicotinate (26156-48-9) → methyl 2-(4-methyloxazol-2-yl)isonicotinate

Conditions	Yield
Stage #1: 4-methyloxazole With n-butyllithium In tetrahydrofuran at -78℃; for 0.166667h; Stage #2: With zinc(II) chloride In tetrahydrofuran at -78 - 20℃; Stage #3: methyl 2-bromoisonicotinate With tetrakis(triphenylphosphine) palladium(0) In tetrahydrofuran at 60℃; for 0.5h; Inert atmosphere; Microwave irradiation;	45%

4-methyloxazole (693-93-6) + (2-amino-6-bromo-3-nitro-pyridin-4-yl)-(6-trifluoromethyl-pyridin-3-ylmethyl)-carbamic acid ethyl ester (947145-70-2) → [2-amino-6-(4-methyl-oxazol-2-yl)-3-nitro-pyridin-4-yl]-(6-trifluoromethyl-pyridin-3-ylmethyl)-carbamic acid ethyl ester (947145-78-0)

Conditions

Yield

Stage #1: 4-methyloxazole With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.166667h; Stage #2: With zinc(II) chloride In tetrahydrofuran; hexane at -78℃; for 0.25h; Stage #3: (2-amino-6-bromo-3-nitro-pyridin-4-yl)-(6-trifluoromethyl-pyridin-3-ylmethyl)-carbamic acid ethyl ester With bis-triphenylphosphine-palladium(II) chloride In tetrahydrofuran; hexane at 90℃; for 0.0833333h; Negishi coupling reaction; Inert atmosphere; Microwave irradiation;

44%

4-methyloxazole (693-93-6) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → 4-methyl-5-oxazolecarboxaldehyde

Conditions	Yield
With n-butyllithium In diethyl ether; hexane at -70 - 20℃; for 2h; Inert atmosphere;	40%
With n-butyllithium 1.) THF, -75 deg C, 45 min, 2.) THF, from -75 deg C to RT; Yield given. Multistep reaction;
Stage #1: 4-methyloxazole With n-butyllithium In tetrahydrofuran at -78℃; for 0.75h; Inert atmosphere; Stage #2: N,N-dimethyl-formamide In tetrahydrofuran at 20℃;

4-methyloxazole (693-93-6) + 8-(1-ethyl-propyl)-3-iodo-2,6-dimethyl-imidazo[1,2-b]pyridazine (910552-65-7) → 8-(1-ethyl-propyl)-2,6-dimethyl-3-(4-methyl-oxazol-5-yl)-imidazo[1,2-b]pyridazine

Conditions	Yield
With caesium carbonate; tris-(dibenzylideneacetone)dipalladium(0); triphenylphosphine In N,N-dimethyl-formamide at 130℃;	39%

4-methyloxazole (693-93-6) + methyl 3-<1'-chlorocyclopropyl>propiolate (83662-44-6) → 4-(1-Chlorcyclopropyl)-3-furancarbonsaeure-methylester (104462-97-7)

Conditions	Yield
In toluene at 150℃; for 18h;	30%

4-methyloxazole (693-93-6) + benzaldehyde (100-52-7) → (4-Methyl-oxazol-2-yl)-phenyl-methanol (90892-90-3)

Conditions	Yield
With n-butyllithium In diethyl ether at -78℃;	30%
With n-butyllithium 1.) hexane, Et2O, 1 h; Yield given. Multistep reaction;

4-methyloxazole (693-93-6) + 4,7-dihydro-2-(4,7-dihydro-1,3-dioxepin-2-yl)-5-nitro-1,3-dioxepin → 1,5-dihydro-3-(4,7-dihydro-1,3-dioxepin-2-yl)-9-hydroxy-8-methyl-3H-<1,3>dioxepino<5,6-c>pyridine (187467-53-4)

Conditions	Yield
With perchloric acid for 4h; Heating;	27.7%

4-methyloxazole (693-93-6) + 4,7-dihydro-2-<3-(4,7-dihydro-1,3-dioxepin-2-yl)-propyl>-1,3-dioxepin (10192-66-2) → 7-[3-(4,7-Dihydro-[1,3]dioxepin-2-yl)-propyl]-3-methyl-5,9-dihydro-6,8-dioxa-2-aza-benzocyclohepten-4-ol (187467-61-4) + 3-[3-(1,5-dihydro-9-hydroxy-8-methyl-3H-[1,3]dioxepino[5,6-c]pyridin-3-yl)-propyl]-1,5-dihydro-9-hydroxy-8-methyl-3H-[1,3]dioxepino[5,6-c]pyridine

Conditions	Yield
With acetic anhydride; nitrobenzene; hydroquinone at 180 - 190℃; for 2h;	A 23.6% B 11.9%

4-methyloxazole (693-93-6) + 6-chloro-4-iodo-1-(phenylsulfonyl)-1H-indazole (1254036-94-6) → 2-(6-chloro-1-(phenylsulfonyl)-1H-indazol-4-yl)-4-methyloxazole

Conditions	Yield
Stage #1: 4-methyloxazole With n-butyllithium In tetrahydrofuran; hexane at -70℃; for 0.5h; Stage #2: 6-chloro-4-iodo-1-(phenylsulfonyl)-1H-indazole With tetrakis(triphenylphosphine) palladium(0); zinc(II) chloride In tetrahydrofuran; hexane at 0℃; for 7h; Reflux;	22%

4-methyloxazole (693-93-6) + 2-bromopentan-3-one (815-52-1) → 2-(2,2,3,3-Tetrafluorpropoxy)-3-pentanon (109308-43-2) + endo-2,endo-4,7-Trimethyl-8-oxa-6-azabicyclo<3.2.1>oct-6-en-3-on (109308-56-7)

Conditions	Yield
With 2,2,3,3-tetrafluoropropanol; sodium 2,2,3,3-tetrafluoropropan-1-olate for 19h;	A 12% B 13%

4-methyloxazole (693-93-6) + chloroformic acid ethyl ester (541-41-3) → methyl 4-methyloxazole-2-carboxylate (1429559-59-0)

Conditions	Yield
Stage #1: 4-methyloxazole With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Inert atmosphere; Stage #2: chloroformic acid ethyl ester In tetrahydrofuran; hexane at -78 - 20℃;	13%

Upstream product

• 116-09-6 hydroxy-2-propanone 
• 583-59-5 2-Methylcyclohexanol 
• 4128-31-8 rac-octan-2-ol 
• 2510-32-9 4-methyl-1,3-oxazole-5-carboxylic acid 

Downstream Products

• 1060816-11-6 2-bromo-4-methyloxazole 
• 616239-57-7 4-methyl-2-(tributylstannyl)oxazole 
• 83081-31-6 4-methyl-2-(p-tolyl)oxazole 
• 947145-82-6 [2-amino-6-(4-methyl-oxazol-2-yl)-3-nitro-pyridin-4-yl]-(3-cyano-benzyl)-carbamic acid ethyl ester 
• 110-00-9 furan 
• 30614-77-8 diethyl 3,4-furandicarboxylate 
• 954-54-1 3,4-diphenylfuran 
• 104462-89-7 4-Cyclopropyl-3-furancarbonsaeure-methylester 
• 75-05-8 acetonitrile 
• 90892-90-3 (4-Methyl-oxazol-2-yl)-phenyl-methanol 
• 104462-97-7 4-(1-Chlorcyclopropyl)-3-furancarbonsaeure-methylester 
• 118559-25-4 1-[4-(4-Methyl-oxazol-2-yl)-phenyl]-ethanone 
• 30614-73-4 3,4-furan-dimethanol diacetate 
• 56286-84-1 3-trifluoromethyl furan 

Relevant articles and documents

Widely Exploited, Yet Unreported: Regiocontrolled Synthesis and the Suzuki–Miyaura Reactions of Bromooxazole Building Blocks

An approach to synthesis of 2-, 4-, and 5-bromooxazoles is described. The method was optimized, and its scope was extended to all three isomeric parents, as well as various alkyl- and aryl-substituted bromooxazoles. It was found that direct regiocontrolled lithiation followed by reaction with electrophilic bromine source was common for all substrates and led exclusively to the target substituted 2-, 4- and 5-bromooxazoles on multigram scale. The utility of the multipurpose building blocks obtained in this work was demonstrated in the Suzuki–Miyaura cross-coupling reaction under parallel synthesis conditions.