7149-65-7

Basic information

• Product Name: Ethyl L-pyroglutamate
• Synonyms: ETHYL L-PYROGLUTAMATE;ETHYL (S)-PYROGLUTAMATE;ETHYL (S)-2-PYRROLIDINONE-5-CARBOXYLATE;ETHYL (S)-(+)-2-PYRROLIDONE-5-CARBOXYLATE;ETHYL (S)-2-PYRROLIDONE-5-CARBOXYLATE;H-PYR-OET;(+)-L-PYROGLUTAMIC ACID ETHYL ESTER;L-PYROGLUTAMIC ACID ETHYL ESTER
• CAS NO: 7149-65-7
• Molecular Formula: C₇H₁₁NO₃
• Molecular Weight: 157.17
• EINECS: 230-480-9
• Product Categories: pharmacetical;Pyroglutamic acid [Pyr, pGu];Chiral Reagents;Heterocycles;Miscellaneous Reagents
• Mol File: 7149-65-7.mol
• Article Data: 51

Chemical Properties

• Melting Point: 54-56 °C
• Boiling Point: 176 °C12 mm Hg(lit.)
• Flash Point: >230 °F
• Appearance: White to cream/Low Melting Solid
• Density: 1.2483 (rough estimate)
• Refractive Index: 1.4310 (estimate)
• Storage Temp.: 0-6°C
• PKA: 14.78±0.40(Predicted)
• BRN: 82621
• CAS DataBase Reference: Ethyl L-pyroglutamate(CAS DataBase Reference)
• NIST Chemistry Reference: Ethyl L-pyroglutamate(7149-65-7)
• EPA Substance Registry System: Ethyl L-pyroglutamate(7149-65-7)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36-37/39
• WGK Germany: 3
• F: 3-10
• Hazardous Substances Data: 7149-65-7(Hazardous Substances Data)

Usage

Chemical Properties

White to cream low melting solid

Uses

(S)-(+)-5-Ethylcarboxyl-2-pyrrolidinone (cas# 7149-65-7) is a compound useful in organic synthesis.

InChI:InChI=1/C7H11NO3/c1-2-11-7(10)5-3-4-6(9)8-5/h5H,2-4H2,1H3,(H,8,9)

Synthetic route

ethanol (64-17-5) + (S,S)-1,7-diazatricyclo[7.3.0.07,11]dodecane-2,6,8,12-tetrone (14842-41-2) → ethyl (S)-pyroglutamate (7149-65-7)

Conditions	Yield
With potassium cyanide for 4h;	100%

ethanol (64-17-5) + L-Pyroglutamic acid (98-79-3) → ethyl (S)-pyroglutamate (7149-65-7)

Conditions	Yield
With thionyl chloride at 0 - 20℃;	99%
With thionyl chloride at 0℃; for 15h;	99%
With thionyl chloride at -5 - 20℃; for 10h;	98%

ethanol (64-17-5) + L-glutamic acid (56-86-0) → ethyl (S)-pyroglutamate (7149-65-7)

Conditions	Yield
With thionyl chloride Heating;	95%
With thionyl chloride 1.) r. t., 1 h, 2.) reflux, 0.5 h;	87%
With thionyl chloride 1) room temperature, 1 h; 2) reflux, 0.5 h;	87%

ethyl iodide (75-03-6) + L-Pyroglutamic acid (98-79-3) → ethyl (S)-pyroglutamate (7149-65-7)

Conditions	Yield
With potassium carbonate In dichloromethane at 0 - 20℃; for 6h;	92%
With N-ethyl-N,N-diisopropylamine In acetonitrile at 10 - 20℃; for 72h;

L-glutamic acid (56-86-0) → ethyl (S)-pyroglutamate (7149-65-7)

Conditions	Yield
With thionyl chloride In ethanol 1) 0 deg C; 2) 1 h, room temp., then 0.5 h reflux;	84%
With thionyl chloride In ethanol; water
Multi-step reaction with 2 steps 1: 0.83 h / 220 - 290 °C / Autoclave; Large scale 2: toluene-4-sulfonic acid / methanol / -5 - 45 °C View Scheme

ethanol (64-17-5) + (S)-5-oxopyrrolidine-2-carbonyl chloride (74936-93-9) → ethyl (S)-pyroglutamate (7149-65-7)

Conditions	Yield
In dichloromethane for 0.0833333h; Heating;	81%

L-glutamic acid diethyl ester (16450-41-2) → ethyl (S)-pyroglutamate (7149-65-7)

Conditions	Yield
at 150℃; under 15.0015 Torr; Inert atmosphere;

di-tert-butyl dicarbonate (24424-99-5) + ethyl (S)-pyroglutamate (7149-65-7) → (S)-ethyl N-tert-butoxycarbonylpyroglutamate (144978-35-8, 144978-12-1)

Conditions	Yield
With dmap In acetonitrile at 20℃;	100%
With dmap In dichloromethane at 20℃; for 6h;	100%
With dmap In acetonitrile at 20℃; for 3h;	98%

2-bromobenzaldehyde O-(phenylmethyl)oxime (902137-35-3) + ethyl (S)-pyroglutamate (7149-65-7) → (S)-1-[2-(Benzyloxyimino-methyl)-phenyl]-5-oxo-pyrrolidine-2-carboxylic acid ethyl ester (902137-36-4)

Conditions	Yield
With caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; tris(dibenzylideneacetone)dipalladium (0) In 1,4-dioxane at 100℃;	99%

2-bromobenzaldehyde O-(phenylmethyl)oxime (902137-35-3) + ethyl (S)-pyroglutamate (7149-65-7) → (S)-5-oxo-1-[2-[(E)-(phenylmethoxyimino)methyl]phenyl]proline ethyl ester (1032651-69-6)

Conditions	Yield
With caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; tris(dibenzylideneacetone)dipalladium (0) In 1,4-dioxane at 100℃; for 8h;	99%

methyl 4-bromo-3-[(phenylmethoxyimino)methyl]benzoate (902137-32-0) + ethyl (S)-pyroglutamate (7149-65-7) → (S)-1-[2-(Benzyloxyimino-methyl)-4-methoxycarbonyl-phenyl]-5-oxo-pyrrolidine-2-carboxylic acid ethyl ester (902137-42-2)

Conditions	Yield
With caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; tris(dibenzylideneacetone)dipalladium (0) In 1,4-dioxane at 100℃;	98%

methyl 4-bromo-3-[(phenylmethoxyimino)methyl]benzoate (902137-32-0) + ethyl (S)-pyroglutamate (7149-65-7) → (S)-1-[4-(methoxycarbonyl)-2-[(E)-(phenylmethoxyimino)methyl]phenyl]-5-oxoproline ethyl ester (1032651-88-9)

Conditions	Yield
With caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; tris(dibenzylideneacetone)dipalladium (0) In 1,4-dioxane at 100℃; for 8h;	98%

triethyloxonium fluoroborate (368-39-8) + ethyl (S)-pyroglutamate (7149-65-7) → ethyl (2S)-5-ethoxy-3,4-dihydro-2H-pyrrole-2-carboxylate (76529-79-8)

Conditions	Yield
With trifluoroacetic acid In dichloromethane at 20℃; for 12h; regioselective reaction;	97%
	92%
In dichloromethane at 20℃; for 40h;	92%
In chloroform at 5℃; for 4h;	69%
In dichloromethane at 20℃; for 168h;	56%

ethyl bromoacetate (105-36-2) + ethyl (S)-pyroglutamate (7149-65-7) → L-1-<(Ethoxycarbonyl)methyl>-5-oxoprolin-ethylester (100462-35-9)

Conditions	Yield
With sodium hydride In tetrahydrofuran; paraffin at 0℃; 20-30 min;	97%
With sodium hydride 1.) benzene, r.t., 30 min; 50-60 deg C, 10 min, 2.) r.t., 2 h; Yield given. Multistep reaction;

ethyl (S)-pyroglutamate (7149-65-7) → (S)-Pyroglutaminol (17342-08-4)

Conditions	Yield
With potassium borohydride; lithium chloride In tetrahydrofuran at -15 - 20℃; for 2h; Reagent/catalyst;	95%
With lithium borohydride In tetrahydrofuran at 20℃; for 48h;	90%
With sodium tetrahydroborate In ethanol	83%

phosgene (75-44-5) + ethyl (S)-pyroglutamate (7149-65-7) → L-1-(chlorocarbonyl)proline ethyl ester (86050-92-2)

Conditions	Yield
In chloroform at 5 - 40℃; for 29h;	95%

benzyl bromide (100-39-0) + ethyl (S)-pyroglutamate (7149-65-7) → (S)-(+)-1-(benzyl)-5-oxopyrrolidine-2-carboxylic acid ethyl ester (137641-62-4)

Conditions	Yield
With sodium hydride In tetrahydrofuran; paraffin at 0℃; 20-30 min;	95%
With sodium hydride 1) THF, mineral oil, 0.25 h, 2) THF, mineral oil, room temperature, 2 h; Yield given. Multistep reaction;
With potassium tert-butylate In tetrahydrofuran; water; ethyl acetate
With tert-BuOK In tetrahydrofuran; water; ethyl acetate
With potassium tert-butylate In tetrahydrofuran at 0 - 20℃; for 24.5h;

methyl chloroformate (79-22-1) + ethyl (S)-pyroglutamate (7149-65-7) → ethyl N-methoxycarbonyl-L-pyroglutamate (261177-52-0)

Conditions	Yield
With dmap; N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 8h;	95%

allyl bromide (106-95-6) + ethyl (S)-pyroglutamate (7149-65-7) → (S)-1-allyl-5-oxo-pyrrolidine-2-carboxylic acid ethyl ester (115445-33-5)

Conditions	Yield
With sodium hydride In tetrahydrofuran; paraffin at 0℃; 20-30 min;	94%
With potassium hydroxide; tetrabutylammomium bromide In tetrahydrofuran sonication (ultrasonic cleaning bath);	81%
With sodium hydride In tetrahydrofuran at 20℃;	80%
With potassium hydroxide; tetra-(n-butyl)ammonium iodide In tetrahydrofuran Ambient temperature; sonic bath;	78%
With potassium hydroxide; tetra-(n-butyl)ammonium iodide In tetrahydrofuran Ambient temperature; sonication;	43%

1,3-dibromopropene (627-15-6) + ethyl (S)-pyroglutamate (7149-65-7) → 1-(3-bromo-2-propenyl)-5-oxoproline ethyl ester

Conditions	Yield
With sodium hydride In tetrahydrofuran; paraffin at 0℃; 20-30 min;	93%

carbon monoxide (201230-82-2) + 2-(2-iodophenyl)acetonitrile (40400-15-5) + ethyl (S)-pyroglutamate (7149-65-7) → (S)-ethyl 10-cyano-5-oxo-1,2,3,5-tetrahydropyrrolo[1,2-b]isoquinoline-3-carboxylate (1075683-99-6)

Conditions	Yield
With palladium diacetate; potassium carbonate; triphenylphosphine In tetrahydrofuran at 80℃; under 10343.2 Torr; for 24h; Autoclave;	93%

ethyl (S)-pyroglutamate (7149-65-7) → ethyl (2S)-5-thioxo-3,4-dihydro-5H-pyrrole-2-carboxylate (80442-95-1)

Conditions	Yield
With Lawessons reagent In toluene for 1h; Heating;	92%
With Lawessons reagent In tetrahydrofuran Ambient temperature;	90%
With Lawessons reagent In tetrahydrofuran at 20℃; for 1h;	90%

ethyl (S)-pyroglutamate (7149-65-7) + methyl iodide (74-88-4) → 1-methyl-L-pyroglutamic acid ethyl ester

Conditions	Yield
With sodium hydride In tetrahydrofuran; paraffin at 0℃; 20-30 min;	92%
With sodium hydride Yield given. Multistep reaction;
With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃;
Stage #1: ethyl (S)-pyroglutamate With sodium hydride In tetrahydrofuran; mineral oil at 20℃; for 0.25h; Stage #2: methyl iodide In tetrahydrofuran; mineral oil at 20℃; for 96h;

carbon monoxide (201230-82-2) + ethyl 2-(2-iodophenyl)acetate (90794-29-9) + ethyl (S)-pyroglutamate (7149-65-7) → (S)-diethyl 5-oxo-1,2,3,5-tetrahydropyrrolo[1,2-b]isoquinoline-3,10-dicarboxylate (1075683-90-7)

Conditions	Yield
With palladium diacetate; potassium carbonate; triphenylphosphine In tetrahydrofuran at 80℃; under 10343.2 Torr; for 24h; Autoclave;	92%

2-carbomethoxyaniline (134-20-3) + ethyl (S)-pyroglutamate (7149-65-7) → 9-oxo-1,2,3,9-tetrahydro-pyrrolo[2,1-b]quinazoline-1-carboxylic acid ethyl ester (866925-48-6)

Conditions	Yield
With trichlorophosphate In 1,2-dichloro-ethane for 3h; Heating;	91%

carbon monoxide (201230-82-2) + ethyl (S)-pyroglutamate (7149-65-7) + ethyl 2-(3,4-methylenedioxy-6-iodophenyl)acetate → (S)-diethyl 5-oxo-5,7,8,9-tetrahydro-[1,3]dioxolo[4,5-g]pyrrolo[1,2-b]isoquinoline-7,10-dicarboxylate (1075683-97-4)

Conditions	Yield
With palladium diacetate; caesium carbonate; triphenylphosphine In tetrahydrofuran at 80℃; under 10343.2 Torr; for 24h; Autoclave;	90%

phenyl isocyanate (103-71-9) + ethyl (S)-pyroglutamate (7149-65-7) → 1-phenyl-2,7-dioxo-[1,3]diazepane-4-carboxylic acid ethyl ester

Conditions	Yield
With sodium hydride In tetrahydrofuran at 20℃;	89%

phenyl isocyanate (103-71-9) + ethyl (S)-pyroglutamate (7149-65-7) → ethyl 3-(2,5-dioxo-1-phenyl-imidazolidin-4-yl)propanoate

Conditions	Yield
With sodium hydride In tetrahydrofuran at 20℃; for 16h;	89%

phenyl isocyanate (103-71-9) + ethyl (S)-pyroglutamate (7149-65-7) → (2S)-ethyl 1-Phenylcarbamoyl-5-oxopyrrolidine-2-carboxylate

Conditions	Yield
With sodium hydride In diethyl ether at 20℃; for 1h;	89%

chloroformic acid ethyl ester (541-41-3) + ethyl (S)-pyroglutamate (7149-65-7) → ethyl (S)-N-(ethoxycarbonyl)pyroglutamate (125048-82-0)

Conditions	Yield
With dmap; N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 8h;	88%

benzyl isothiocyanate (3173-56-6) + ethyl (S)-pyroglutamate (7149-65-7) → 1-benzyl-2,7-dioxo-[1,3]diazepane-4-carboxylic acid ethyl ester

Conditions	Yield
With sodium hydride In tetrahydrofuran at 20℃;	87%

benzyl isothiocyanate (3173-56-6) + ethyl (S)-pyroglutamate (7149-65-7) → ethyl 3-(1-benzyl-2,5-dioxo-imidazolidin-4-yl)propanoate

Conditions	Yield
With sodium hydride In tetrahydrofuran at 20℃; for 16h;	87%

(fluorenylmethoxy)carbonyl chloride (28920-43-6) + ethyl (S)-pyroglutamate (7149-65-7) → 1-(9H-fluoren-9-ylmethyl) 2-ethyl 5-oxopyrrolidine-1,2-dicarboxylate

Conditions	Yield
Stage #1: ethyl (S)-pyroglutamate With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 0.333333h; Inert atmosphere; Stage #2: (fluorenylmethoxy)carbonyl chloride In tetrahydrofuran at -78 - 20℃; for 20h; Inert atmosphere;	87%
Stage #1: ethyl (S)-pyroglutamate With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; Inert atmosphere; Stage #2: (fluorenylmethoxy)carbonyl chloride In tetrahydrofuran at -78 - 20℃; for 20h; Inert atmosphere;	87%
Stage #1: ethyl (S)-pyroglutamate With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 0.25h; Inert atmosphere; Stage #2: (fluorenylmethoxy)carbonyl chloride In tetrahydrofuran at -78 - 20℃; for 16h; Inert atmosphere; Stage #3: With ammonium chloride In tetrahydrofuran; water	83%

Upstream product

• 64-17-5 ethanol 
• 56-86-0 L-glutamic acid 
• 98-79-3 L-Pyroglutamic acid 
• 14842-41-2 (S,S)-1,7-diazatricyclo[7.3.0.0^7,11]dodecane-2,6,8,12-tetrone 
• 75-03-6 ethyl iodide 
• 97717-45-8 L-trimethylsilyl pyroglutamate 
• 74936-93-9 (S)-5-oxopyrrolidine-2-carbonyl chloride 
• 1118-89-4 diethyl-L-glutamate hydrochloride 
• 16450-41-2 L-glutamic acid diethyl ester 
• 115445-33-5 (S)-1-allyl-5-oxo-pyrrolidine-2-carboxylic acid ethyl ester 

Downstream Products

• 51693-17-5 (S)-toluene-4-sulfonic acid 5-oxo-pyrrolidin-2-ylmethyl ester 
• 80442-95-1 ethyl (2S)-5-thioxo-3,4-dihydro-5H-pyrrole-2-carboxylate 
• 144978-35-8 (S)-ethyl N-tert-butoxycarbonylpyroglutamate 
• 188548-07-4 5-Oxo-2-phenethyl-pyrrolidine-2-carboxylic acid ethyl ester 
• 188548-06-3 ethyl 2-benzylpyroglutamate 
• 149561-81-9 (-)-(S)-5-(Hydroxydiphenylmethyl)pyrrolidin-2-one 
• 172879-74-2 ethyl (S)-3,4-dihydro-2H-pyrrole-2-carboxylate 
• 62401-18-7 1-(2-propenyl)-5-hydroxymethyl-2-pyrrolidinone 
• 126908-58-5 1-(2-cyclohexenyl)-5-hydroxymethyl-2-pyrrolidinone 
• 126908-56-3 1-(3-phenyl-2-propenyl)-5-hydroxymethyl-2-pyrrolidinone 
• 121873-15-2 unifide 
• 1032651-69-6 (S)-5-oxo-1-[2-[(E)-(phenylmethoxyimino)methyl]phenyl]proline ethyl ester 
• 1032651-88-9 (S)-1-[4-(methoxycarbonyl)-2-[(E)-(phenylmethoxyimino)methyl]phenyl]-5-oxoproline ethyl ester 
• 336818-12-3 ethyl 2-(4-bromobenzyl)-5-oxopyrrolidine-2-carboxylate 

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