766-36-9

Basic information

• Product Name: 3-Ethyl-4-methyl-3-pyrrolin-2-one
• Synonyms: 3-ETHYL-1,5-DIHYDRO-4-METHYL-2H-PYRROL-2-ONE;3-ETHYL-4-METHYL-3-PYROLIN-2-ONE;3-ETHYL-4-METHYL-3-PYRROLIN-2-ONE;3-ETHYL-4-METHYL-3-PYRROLINE-2-ONE;3-ETHYL-4-METHYL-1,5-DIHYDRO-2H-PYRROL-2-ONE;3-ETHYL-4-METHYL-1,5-DIHYDRO-PYRROL-2-ONE;3-ETHYL-4-METHYL-2-OXO-1,5-DIHYDROPYRROL-2-ONE;3-ethyl-4-methyl-2-oxo-3-pyrroline
• CAS NO: 766-36-9
• Molecular Formula: C₇H₁₁NO
• Molecular Weight: 125.17
• EINECS: 1312995-182-4
• Product Categories: pharmacetical;(intermediate of glimepiride);Building Blocks;Heterocyclic Building Blocks;Pyrrolines
• Mol File: 766-36-9.mol
• Article Data: 10

Chemical Properties

• Melting Point: 100-104 °C(lit.)
• Boiling Point: 279 °C at 760 mmHg
• Flash Point: 156.6 °C
• Appearance: light yellow or white crystalline powder
• Density: 0.977 g/cm³
• Vapor Pressure: 0.00413mmHg at 25°C
• Refractive Index: 1.467
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 14.44±0.60(Predicted)
• Water Solubility: Slightly soluble in water.
• CAS DataBase Reference: 3-Ethyl-4-methyl-3-pyrrolin-2-one(CAS DataBase Reference)
• NIST Chemistry Reference: 3-Ethyl-4-methyl-3-pyrrolin-2-one(766-36-9)
• EPA Substance Registry System: 3-Ethyl-4-methyl-3-pyrrolin-2-one(766-36-9)

Safety Data

• Hazard Codes: Xi
• Safety Statements: 22-24/25
• WGK Germany: 3
• Hazardous Substances Data: 766-36-9(Hazardous Substances Data)

Usage

Uses

3-Ethyl-4-methyl-3-pyrrolin-2-one is used as an intermediate for the manufacture of medicines. It is used for the preparation of Glimepiride (G410150), and its intermediates and as antidiabetic agents.

General Description

3-Ethyl-4-methyl-3-pyrrolin-2-one, a five-membered α,β-unsaturated lactam derivative, has various applications in medicinal chemistry. It can be synthesized by employing following as starting materials:allylamine, via palladium(II)-assisted cyclization4-methoxybenzylamine, via a ring-closing-metathesis strategy3-ethyl-1-(4-methoxybenzyl)-4-methyl-1,5-dihydro-2H-pyrrol-2- one

InChI:InChI=1/C7H11NO/c1-3-6-5(2)4-8-7(6)9/h3-4H2,1-2H3,(H,8,9)

Synthetic route

3-ethyl-4-methyl-5-p-toluenesulfonyl-3-pyrrolin-2-one (184422-85-3) → 3-ethyl-4-methyl-3-pyrrolin-2-one (766-36-9)

Conditions	Yield
With sodium tetrahydroborate In ethanol	95%
With sodium tetrahydroborate	76%

1-acetyl-3-ethyl-4-methyl-1,5-dihydro-pyrrol-2-one (61892-80-6) → 3-ethyl-4-methyl-3-pyrrolin-2-one (766-36-9)

Conditions	Yield
With water; sodium carbonate Heating;	90%
With water; sodium carbonate
With hydrogenchloride; methanol

1-benzyl-3-ethyl-4-methyl-1,5-dihydro-2H-pyrrol-2-one → 3-ethyl-4-methyl-3-pyrrolin-2-one (766-36-9)

Conditions	Yield
With trifluorormethanesulfonic acid In toluene at 150℃; for 0.75h; Temperature; Time; Microwave irradiation; Sealed tube;	86%

3-ethyl-1-(4-methoxybenzyl)-4-methyl-1,5-dihydro-2H-pyrrol-2-one → 3-ethyl-4-methyl-3-pyrrolin-2-one (766-36-9)

Conditions	Yield
With methoxybenzene; trifluoroacetic acid at 80℃; for 3h;	81%
With ammonium cerium (IV) nitrate In water; acetonitrile at 20℃; for 2h;	80%

4-acetylamino-2-ethyl-3-hydroxy-3-methyl-butyric acid ethyl ester → 3-ethyl-4-methyl-3-pyrrolin-2-one (766-36-9)

Conditions	Yield
With potassium hydroxide In methanol for 32h; Heating;	75.7%

C12H19NO3 → 3-ethyl-4-methyl-3-pyrrolin-2-one (766-36-9)

Conditions	Yield
With hydrogenchloride In 1,4-dioxane; water; ethyl acetate at 0 - 35℃; for 2h;	75%

3-ethyl-2-formyl-4-methylpyrrole (32928-30-6) → 3-ethyl-4-methyl-3-pyrrolin-2-one (766-36-9)

Conditions	Yield
With dihydrogen peroxide; sodium hydrogencarbonate In methanol at 20℃;	67%

3-ethyl-2-methoxy-4-methyl-pyrrole (408338-28-3) → 3-ethyl-4-methyl-3-pyrrolin-2-one (766-36-9)

Conditions	Yield
With hydrogenchloride; methanol

4-ethyl-5-bromo-3-methyl-pyrrole-2-carboxylic acid (408338-52-3) → 3-ethyl-4-methyl-3-pyrrolin-2-one (766-36-9)

Conditions	Yield
With hydrogenchloride; water
Multi-step reaction with 2 steps 1: aqueous hydrochloric acid 2: hydrogen chloride; methanol View Scheme

3-ethyl-2-formyl-4-methylpyrrole (32928-30-6) → 4-ethyl-3-methyl-1H-pyrrol-2(5H)-one (766-45-0) + 3-ethyl-4-methyl-3-pyrrolin-2-one (766-36-9)

Conditions	Yield
With pyridine; dihydrogen peroxide at 50 - 60℃;

ethyl-α-ethylacetoacetate cyanohydrin (247098-17-5) → 3-ethyl-4-methyl-3-pyrrolin-2-one (766-36-9)

Conditions	Yield
With hydrogen; acetic anhydride; sodium carbonate; T-1 Raney Nickel 1.) EtOH, 33 deg C, 50 psi, 12 h, 2.) reflux, 4 h; Yield given. Multistep reaction;
Multi-step reaction with 2 steps 1: 84 percent / H2 / Raney Ni / 20 °C / 2585.74 Torr 2: 75.7 percent / KOH / methanol / 32 h / Heating View Scheme
Multi-step reaction with 2 steps 1: 15 percent / H2; Ac2O / Ra-Ni / 40 °C / 3800 Torr 2: 90 percent / Na2CO3; H2O / Heating View Scheme
Multi-step reaction with 2 steps 1: Raney nickel; acetic acid / 100 °C / 80905.8 - 95616 Torr / Hydrogenation.Erhitzen de Reaktionsprodukts mit Acetanhydrid 2: methanol; hydrochloric acid View Scheme

Acetic acid 1-acetyl-4-ethyl-3-methyl-5-oxo-pyrrolidin-3-yl ester → 3-ethyl-4-methyl-3-pyrrolin-2-one (766-36-9)

pyridine (110-86-1) + 3-ethyl-2-formyl-4-methylpyrrole (32928-30-6) + water (7732-18-5) + dihydrogen peroxide (7722-84-1) → 4-ethyl-3-methyl-1H-pyrrol-2(5H)-one (766-45-0) + 3-ethyl-4-methyl-3-pyrrolin-2-one (766-36-9)

Conditions	Yield
at 50 - 60℃;

3-ethyl-N-methoxy-N-methyl-4-methylpyrrole-2-carboxamide (910032-52-9) → 3-ethyl-4-methyl-3-pyrrolin-2-one (766-36-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 65 percent / LiAlH4 / tetrahydrofuran / 0 °C 2: 67 percent / NaHCO3; aq. H2O2 / methanol / 20 °C View Scheme

ethyl 2-ethyl-3-oxobutanoate (607-97-6) → 3-ethyl-4-methyl-3-pyrrolin-2-one (766-36-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: 80 percent / dimethylformamide / 0 - 5 °C 2: 15 percent / H2; Ac2O / Ra-Ni / 40 °C / 3800 Torr 3: 90 percent / Na2CO3; H2O / Heating View Scheme
Multi-step reaction with 2 steps 1: 1.) NaHSO3 / 2.) from 0 deg C to RT, 3 h 2: 1.) H2, Ac2O, 2.) aq. Na2CO3 / 1.) T-1 Raney nickel / 1.) EtOH, 33 deg C, 50 psi, 12 h, 2.) reflux, 4 h View Scheme

3-nitropentan-2-ol acetate (89896-01-5) → 3-ethyl-4-methyl-3-pyrrolin-2-one (766-36-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: 53 percent / guanidine / propan-2-ol; tetrahydrofuran / 1 h 2: 97 percent / Br2 / CH2Cl2 / 1 h / 0 °C 3: 81 percent / aq. TFA 4: 95 percent / NaBH4 / ethanol View Scheme

4-ethyl-3-methyl-2-(p-toluenesulfonyl)-1H-pyrrole (171111-15-2) → 3-ethyl-4-methyl-3-pyrrolin-2-one (766-36-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: 97 percent / Br2 / CH2Cl2 / 1 h / 0 °C 2: 81 percent / aq. TFA 3: 95 percent / NaBH4 / ethanol View Scheme
Multi-step reaction with 3 steps 1: phenyltrimethylammonium tribromide / dichloromethane 2: trifluoroacetic acid / water 3: sodium tetrahydroborate View Scheme

2-bromo-3-ethyl-4-methyl-5-p-toluenesulfonyl-pyrrole (226223-25-2) → 3-ethyl-4-methyl-3-pyrrolin-2-one (766-36-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 81 percent / aq. TFA 2: 95 percent / NaBH4 / ethanol View Scheme
Multi-step reaction with 2 steps 1: trifluoroacetic acid / water 2: sodium tetrahydroborate View Scheme

4-ethyl-3-methyl-pyrrole-2-carboxylic acid (23466-29-7) → 3-ethyl-4-methyl-3-pyrrolin-2-one (766-36-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: acetic acid; bromine 2: aqueous hydrochloric acid 3: hydrogen chloride; methanol View Scheme
Multi-step reaction with 2 steps 1: acetic acid; bromine 2: hydrochloric acid; water View Scheme

1-(4-methoxybenzyl)-4-methyl-1,5-dihydro-2H-pyrrol-2-one → 3-ethyl-4-methyl-3-pyrrolin-2-one (766-36-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium hydride / tetrahydrofuran / 0.25 h / 0 °C 1.2: 0 - 20 °C 2.1: ammonium cerium (IV) nitrate / water; acetonitrile / 2 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1.1: sodium hydride / tetrahydrofuran / 0.25 h / 0 °C 1.2: 3 h / 0 °C 2.1: trifluoroacetic acid; methoxybenzene / 3 h / 80 °C View Scheme

N-(4-methoxybenzyl)-N-(2-methylallyl)acrylamide → 3-ethyl-4-methyl-3-pyrrolin-2-one (766-36-9)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: tricyclohexylphosphine[1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidine][benzylidene]ruthenium(II) dichloride; titanium(IV)isopropoxide / toluene / 12 h / 80 °C / Inert atmosphere 2.1: sodium hydride / tetrahydrofuran / 0.25 h / 0 °C 2.2: 0 - 20 °C 3.1: ammonium cerium (IV) nitrate / water; acetonitrile / 2 h / 20 °C View Scheme

ethyl 3-(allyl(4-methoxybenzyl)amino)-3-oxopropanoate → 3-ethyl-4-methyl-3-pyrrolin-2-one (766-36-9)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: copper dichloride; palladium dichloride / N,N-dimethyl-formamide; water / 8 h / 95 °C 2.1: sodium chloride / water; dimethyl sulfoxide / 12 h / 120 - 130 °C 3.1: sodium hydride / tetrahydrofuran / 0.25 h / 0 °C 3.2: 0 - 20 °C 4.1: ammonium cerium (IV) nitrate / water; acetonitrile / 2 h / 20 °C View Scheme

ethyl 1-(4-methoxybenzyl)-4-methyl-2-oxo-2,5-dihydro-1H-pyrrole-3-carboxylate → 3-ethyl-4-methyl-3-pyrrolin-2-one (766-36-9)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium chloride / water; dimethyl sulfoxide / 12 h / 120 - 130 °C 2.1: sodium hydride / tetrahydrofuran / 0.25 h / 0 °C 2.2: 0 - 20 °C 3.1: ammonium cerium (IV) nitrate / water; acetonitrile / 2 h / 20 °C View Scheme

5-hydroxy-4-methyl-5H-furan-2-one (40834-42-2) → 3-ethyl-4-methyl-3-pyrrolin-2-one (766-36-9)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: isopropyl alcohol / 1 h / 40 °C 1.2: 1.5 h / 0 - 25 °C 1.3: 16 h / 50 °C / pH 7-8 2.1: sodium hydride / tetrahydrofuran / 0.25 h / 0 °C 2.2: 3 h / 0 °C 3.1: trifluoroacetic acid; methoxybenzene / 3 h / 80 °C View Scheme
Multi-step reaction with 3 steps 1.1: isopropyl alcohol / 1 h / 40 °C 1.2: 1.5 h / 0 - 25 °C 1.3: 16 h / 50 °C / pH 7-8 2.1: sodium hydride / tetrahydrofuran / 0.25 h / 0 °C 2.2: 3 h / 0 °C 3.1: trifluorormethanesulfonic acid / toluene / 0.75 h / 150 °C / Microwave irradiation; Sealed tube View Scheme

N-(2,2-dimethoxypropyl)butanamide → 3-ethyl-4-methyl-3-pyrrolin-2-one (766-36-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: hydrogenchloride / water / 4 h / 15 - 35 °C 2: dmap / dichloromethane / 10 h / 0 - 30 °C 3: sodium hydroxide / dimethyl sulfoxide / 0.5 h / 15 - 35 °C 4: hydrogenchloride / water; ethyl acetate; 1,4-dioxane / 2 h / 0 - 35 °C View Scheme

N-acetonyl-4-butanoylamine → 3-ethyl-4-methyl-3-pyrrolin-2-one (766-36-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: dmap / dichloromethane / 10 h / 0 - 30 °C 2: sodium hydroxide / dimethyl sulfoxide / 0.5 h / 15 - 35 °C 3: hydrogenchloride / water; ethyl acetate; 1,4-dioxane / 2 h / 0 - 35 °C View Scheme

Upstream product

• 408338-28-3 3-ethyl-2-methoxy-4-methyl-pyrrole 
• 110-86-1 pyridine 
• 32928-30-6 3-ethyl-2-formyl-4-methylpyrrole 
• 7732-18-5 water 
• 7722-84-1 dihydrogen peroxide 
• 171111-15-2 4-ethyl-3-methyl-2-(p-toluenesulfonyl)-1H-pyrrole 
• 226223-25-2 2-bromo-3-ethyl-4-methyl-5-p-toluenesulfonyl-pyrrole 
• 40834-42-2 5-hydroxy-4-methyl-5H-furan-2-one 
• 23466-29-7 4-ethyl-3-methyl-pyrrole-2-carboxylic acid 
• 89896-01-5 3-nitropentan-2-ol acetate 
• 607-97-6 ethyl 2-ethyl-3-oxobutanoate 
• 910032-52-9 3-ethyl-N-methoxy-N-methyl-4-methylpyrrole-2-carboxamide 
• 184422-85-3 3-ethyl-4-methyl-5-p-toluenesulfonyl-3-pyrrolin-2-one 

Downstream Products

• 247098-18-6 3-ethyl-4-methyl-2-oxo-N-(2-phenylethyl)-2,5-dihydro-1H-pyrrole-1-carboxamide 
• 93479-97-1 glimepiride 
• 93479-97-1 glimepiride 
• 951224-94-5 (Z)-3-ethyl-4-methyl-5-((pyridin-2-yl)methylene)-1H-pyrrol-2(5H)-one 
• 1402612-00-3 3-ethyl-4-methyl-1-[(4-methylbenzene)sulfonyl]-2,5-dihydro-1H-pyrrol-2-one 
• 1402612-05-8 3-ethyl-4-methyl-1-[(4-methylbenzene)sulfonyl]-5-(prop-2-en-1-yl)-2-(thiophen-2-yl)-1H-pyrrole 
• 1402612-04-7 3-ethyl-4-methyl-1-[(4-methylbenzene)sulfonyl]-2-phenyl-5-(prop-2-en-1-yl)-1H-pyrrole 
• 1402612-03-6 2-butyl-3-ethyl-4-methyl-1-[(4-methylbenzene)sulfonyl]-5-(prop-2-en-1-yl)-1H-pyrrole 
• 1402612-02-5 4-ethyl-3-methyl-1-[(4-methylbenzene)sulfonyl]-2-(prop-2-en-1-yl)-1H-pyrrole 
• 1402612-01-4 3-ethyl-4-methyl-1-[(4-methylbenzene)sulfonyl]-1H-pyrrol-2-yl prop-2-en-1-yl carbonate 

Relevant articles and documents

Pyrrolinone compound and synthesis method thereof

The invention provides a pyrrolinone compound, the structural formula of the pyrrolinone compound is shown as the formula 1, R1 is selected from one of C1-C5 alkoxy, benzyloxy, C1-C5 alkyl and phenyl;R2 and R3 are respectively and independently selected from one of hydrogen, a C1-C5 alkyl group, a C1-C5 alkoxy group, a C1-C5 alkyl sulfenyl group, a C1-C5 alkyl sulfinyl group, a C1-C5 alkyl sulfonyl group, a phenyl group with different substitutions, a phenoxy group with different substitutions, a thiophenyl group with different substitutions, a benzenesulfinyl group with different substitutions and a benzenesulfonyl group with different substitutions; and n1 and n2 are integers from 1 to 5. The pyrrolinone compound can be used as pharmaceutical intermediates. The invention also provides asynthesis method of the pyrrolinone compound. The method is more suitable for industrialization, lower in cost and milder in synthesis condition.

Synthesis of 3-Ethyl-4-methyl-1,5-dihydro-2H-pyrrol-2-one by Novel Palladium(II)-Catalyzed Cyclization and Ring-Closing Metathesis

Synthesis of 3-ethyl-4-methyl-1,5-dihydro-2H-pyrrol-2-one is described starting from commercially available allylamine and 4-methoxybenzylamine employing palladium-catalyzed cyclization or ring-closing metathesis as the key steps.

Regiocontrolled synthesis of pyrrole-2-carboxaldehydes and 3-pyrrolin-2-ones from pyrrole Weinreb amides

A regiocontrolled synthesis of 3,4-disubstituted pyrrole-2-carboxaldehydes was completed in two steps from acyclic starting materials. A Barton-Zard pyrrole synthesis between N-methoxy-N-methyl-2-isocyanoacetamide and α-nitroalkenes or β-nitroacetates provided N-methoxy-N-methyl pyrrole-2-carboxamides (pyrrole Weinreb amides), which were converted into the corresponding pyrrole-2-carboxaldehydes by treatment with lithium aluminum hydride. A regioselective oxidation of the pyrrole-2-carboxaldehydes gave the corresponding 3,4-disubstituted 3-pyrrolin-2-ones.