22677-21-0

Basic information

• Product Name: 2-Pyrrolidinone,4-hydroxy-, (4R)-
• Synonyms: 2-Pyrrolidinone,4-hydroxy-, (R)- (8CI);(4R)-4-Hydroxy-2-pyrrolidinone;(4R)-4-Hydroxypyrrolidin-2-one;(R)-4-Hydroxy-2-pyrrolidinone;(R)-4-Hydroxypyrrolidin-2-one
• CAS NO: 22677-21-0
• Molecular Formula: C₄H₇NO₂
• Molecular Weight: 101.1039
• Product Categories: Pyrrole&Pyrrolidine&Pyrroline;Amines;Chiral Reagents;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Drug Intermediates
• Mol File: 22677-21-0.mol
• Article Data: 17

Chemical Properties

• Melting Point: 156-160℃
• Boiling Point: 363.6 °C at 760 mmHg
• Flash Point: 173.7 °C
• Appearance: white to light yellow crystal powder
• Density: 1.292 g/cm³
• Vapor Pressure: 9.26E-07mmHg at 25°C
• Refractive Index: 1.513
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: DMSO (Sparingly), Methanol (Slightly), Water (Sparingly)
• PKA: 13.62±0.20(Predicted)
• Water Solubility: Slightly soluble in water.
• BRN: 1524193
• CAS DataBase Reference: 2-Pyrrolidinone,4-hydroxy-, (4R)-(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Pyrrolidinone,4-hydroxy-, (4R)-(22677-21-0)
• EPA Substance Registry System: 2-Pyrrolidinone,4-hydroxy-, (4R)-(22677-21-0)

Safety Data

• Hazard Codes: Xi:Irritant
• Statements: R36/37/38:
• Safety Statements: S26:
• WGK Germany: 3
• Hazardous Substances Data: 22677-21-0(Hazardous Substances Data)

Usage

Chemical Properties

white to light yellow crystal powde

Uses

Different sources of media describe the Uses of 22677-21-0 differently. You can refer to the following data:
1. The (R)-enantiomer intermediate in the preparation of Oxiracetam
2. (R)-(+)-4-Hydroxy-2-pyrrolidinone intermediate in the preparation of Oxiracetam. Also used as enantiomeric intermediate for the asymmetric single isomeric drugs including antitumor, anesthetic, antipasmodic, anti-inflammatory or anti-HIV activity products.

InChI:InChI=1/C4H7NO2/c6-3-1-4(7)5-2-3/h3,6H,1-2H2,(H,5,7)/t3-/m1/s1

Synthetic route

ethyl (L)-4-chloro-3-hydroxybutyrate (10488-69-4, 86728-85-0, 87068-18-6, 90866-33-4) → (R)-4-hydroxy-2-pyrrolidinone (22677-21-0)

Conditions	Yield
With ammonium hydroxide at 80℃; for 3h;	82%

1-(1'-phenylethyl)-4-phenylmethoxypyrrolidin-2-one (135056-42-7) → (R)-4-hydroxy-2-pyrrolidinone (22677-21-0)

Conditions	Yield
With ammonia; sodium In tetrahydrofuran for 1h;	51%

(4R)-4-hydroxy-1-<(1S)-1-phenylethyl>pyrrolidin-2-one (131653-48-0) → (R)-4-hydroxy-2-pyrrolidinone (22677-21-0)

Conditions	Yield
With ammonia; lithium In tetrahydrofuran; tert-butyl alcohol at -60℃; for 0.25h;

(R)-4-Hydroxy-4,5-dihydro-3H-pyrrole-2-carboxylic acid anion → (R)-4-hydroxy-2-pyrrolidinone (22677-21-0)

Conditions	Yield
With sulfuric acid; dihydrogen peroxide at 40℃; for 0.75h; Yield given;

ethyl (R)-4-amino-3-hydroxybutanoate hydrochloride → (R)-4-hydroxy-2-pyrrolidinone (22677-21-0)

3(R)-hydroxy-4-aminobutyric acid ethyl ester (208103-39-3) → (R)-4-hydroxy-2-pyrrolidinone (22677-21-0)

Conditions	Yield
In ethanol

Ru2Cl4((S)-BINAP)2·NEt3in + ammonium salt of methyl 4-amino-3-oxobutanoate → (R)-4-hydroxy-2-pyrrolidinone (22677-21-0)

Conditions	Yield
In methanol

(R)-4-hydroxy-2-pyrrolidinone (22677-21-0) + tert-butyldimethylsilyl chloride (18162-48-6) → (4R)-4-((tert-butyl(dimethyl)silyl)oxy)pyrrolidin-2-one (131653-51-5)

Conditions	Yield
With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 0.5h; Condensation;	99%
With 1H-imidazole In N,N-dimethyl-formamide at 0 - 20℃; for 12h;	95%
With 1H-imidazole In N,N-dimethyl-formamide at 0 - 20℃; for 3h;	91%

(R)-4-hydroxy-2-pyrrolidinone (22677-21-0) + tert-butylchlorodiphenylsilane (58479-61-1) → (R)-4-[tert-butyl(diphenyl)silanyloxy]pyrrolidin-2-one (945635-00-7)

Conditions	Yield
With 1H-imidazole In N,N-dimethyl-formamide at 0℃; for 0.5h;	96%

(R)-4-hydroxy-2-pyrrolidinone (22677-21-0) → (R)-4-Amino-3-hydroxybutanoic acid (7013-07-2)

Conditions	Yield
With hydrogenchloride for 4h; Heating;	94%
With lithium hydroxide for 24h; Ambient temperature;	89%
With hydrogenchloride for 2h; Heating;	70%
With barium dihydroxide
With hydrogenchloride for 10h; Heating; Yield given;

(R)-4-hydroxy-2-pyrrolidinone (22677-21-0) + triisopropylsilyl chloride (13154-24-0) → C13H27NO2Si

Conditions	Yield
With 1H-imidazole In dichloromethane at 20℃; Cooling with ice;	81%

4-(4,6-dichloropyridin-2-yl)morpholine (852333-59-6) + (R)-4-hydroxy-2-pyrrolidinone (22677-21-0) → (4R)-1-[4-chloro-6-(morpholin-4-yl)pyridin-2-yl]-4-hydroxypyrrolidin-2-one

Conditions	Yield
With tris(dibenzylideneacetone)dipalladium(0) chloroform complex; sodium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane; water at 100℃; for 2h; Inert atmosphere;	78%

lauric acid (143-07-7) + (R)-4-hydroxy-2-pyrrolidinone (22677-21-0) → (R)-4-lauroyloxy-2-pyrrolidinone

Conditions	Yield
With pyridine; dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 48h;	60%

(R)-4-hydroxy-2-pyrrolidinone (22677-21-0) + 7-bromo-2-(difluoro(4-fluorophenyl)methyl)-4-(methylthio)quinazoline (1362910-89-1) → (R)-1-(2-(difluoro(4-fluorophenyl)methyl)-4-(methylthio)quinazolin-7-yl)-4-hydroxypyrrolidin-2-one (1362910-95-9)

Conditions	Yield
With caesium carbonate; tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane at 100℃; Inert atmosphere;	48%

(R)-4-hydroxy-2-pyrrolidinone (22677-21-0) + 7-chloro-1-(2,4-difluorophenyl)-4-oxo-N-[(2S)-1,1,1-trifluorobutan-2-yl]-1,4-dihydro-1,8-naphthyridine-3-carboxamide → 1-(2,4-difluorophenyl)-7-[(4R)-4-hydroxy-2-oxopyrrolidin-1-yl]-4-oxo-N-[(2S)-1,1,1-trifluorobutan-2-yl]-1,4-dihydro-1,8-naphthyridine-3-carboxamide

Conditions	Yield
With palladium diacetate; potassium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane at 80℃; Inert atmosphere;	39%

(R)-4-hydroxy-2-pyrrolidinone (22677-21-0) + 1-bromo-4-iodo-2-methylbenzene (202865-85-8) → (R)-1-(4-bromo-3-methyl-phenyl)-4-hydroxy-pyrrolidin-2-one (1253926-33-8)

Conditions	Yield
With caesium carbonate; tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane at 110℃; Inert atmosphere;	38%

(R)-4-hydroxy-2-pyrrolidinone (22677-21-0) → (S)-4-azidopyrrolidin-2-one (899806-32-7)

Conditions	Yield
Stage #1: (R)-4-hydroxy-2-pyrrolidinone With methanesulfonyl chloride; triethylamine In dichloromethane at 20℃; for 1h; Stage #2: With sodium azide In N,N-dimethyl-formamide at 60℃; for 3h;	32%

(R)-4-hydroxy-2-pyrrolidinone (22677-21-0) + 1-Chloro-4-(chloromethyl)benzene (104-83-6) → (R)-4-[(4-chlorobenzyl)oxy]-2-pyrrolidinone

Conditions	Yield
Stage #1: (R)-4-hydroxy-2-pyrrolidinone With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.25h; Stage #2: 1-Chloro-4-(chloromethyl)benzene In N,N-dimethyl-formamide at 20℃;	30%

(R)-4-hydroxy-2-pyrrolidinone (22677-21-0) + ethyl bromoacetate (105-36-2) → ethyl (R)-4-hydroxy-2-oxo-1-pyrrolidineacetate (68252-27-7)

Conditions	Yield
With sodium hydride; 1,1,1,3,3,3-hexamethyl-disilazane 1) reflux, 2 h; 2) acetonitrile, reflux, 30 min; Multistep reaction;

methanol (67-56-1) + (R)-4-hydroxy-2-pyrrolidinone (22677-21-0) → (R)-4-Hydroxy-5-methoxy-pyrrolidin-2-one

Conditions	Yield
With sodium phenylsulfonate at 15℃; Product distribution; Further Variations:; Reagents; electrode material; current density; Oxidation; methoxylation; Electrochemical reaction;
With sodium phenylsulfonate at 15℃; Oxidation; methoxylation; Electrochemical reaction;
With sodium phenylsulfonate at 20℃; Etherification; Electrolysis;

(R)-4-hydroxy-2-pyrrolidinone (22677-21-0) + t-BuMe2SiX → (4R)-4-((tert-butyl(dimethyl)silyl)oxy)pyrrolidin-2-one (131653-51-5)

Conditions	Yield
Substitution;

(R)-4-hydroxy-2-pyrrolidinone (22677-21-0) + [2-(4-(bromomethyl)phenyl)ethyl]carbamic acid tert-butyl ester (914103-95-0) → tert-butyl [2-(4-{[(4R)-4-hydroxy-2-oxopyrrolidin-1-yl]methyl}phenyl)ethyl]carbamate (914104-03-3)

Conditions	Yield
Stage #1: (R)-4-hydroxy-2-pyrrolidinone; [2-(4-(bromomethyl)phenyl)ethyl]carbamic acid tert-butyl ester With sodium hydride In N,N-dimethyl-formamide at 1 - 30℃; for 1h; Stage #2: With potassium hydrogensulfate; water In ethyl acetate; N,N-dimethyl-formamide

(R)-4-hydroxy-2-pyrrolidinone (22677-21-0) + thioacetic acid (507-09-5) + diethylazodicarboxylate (1972-28-7) → (4S)-4-acetylthio-2-pyrrolidone

Conditions	Yield
With triphenylphosphine In tetrahydrofuran
With triphenylphosphine In tetrahydrofuran

6-bromo-N-[(2,6-dimethylphenyl)methyl]-2,3-dimethylimidazo[1,2-a]pyridin-8-amine (212267-75-9) + (R)-4-hydroxy-2-pyrrolidinone (22677-21-0) → (4R)-1-(8-{[(2,6-dimethylphenyl)methyl]amino}-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-4-hydroxy-2-pyrrolidinone

Conditions	Yield
With potassium carbonate; N,N`-dimethylethylenediamine; copper(l) iodide In 1,4-dioxane at 140℃; for 14h; Ullmann-type coupling; Microwave synthesizer;

(R)-4-hydroxy-2-pyrrolidinone (22677-21-0) + methyl iodide (74-88-4) → 4-methoxy-1-methylpyrrolidin-2-one (787636-39-9)

Conditions	Yield
Stage #1: (R)-4-hydroxy-2-pyrrolidinone With sodium hydride In tetrahydrofuran at 20 - 50℃; for 22h; Stage #2: methyl iodide In tetrahydrofuran at 20℃; for 70h;

(R)-4-hydroxy-2-pyrrolidinone (22677-21-0) + 4-(4-bromo-6-methylquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide (1422497-68-4) → (4R)-1-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-4-hydroxypyrrolidin-2-one (1422500-11-5)

Conditions	Yield
With copper(l) iodide; (R,R)-N,N'-dimethyl-1,2-diaminocyclohexane; potassium carbonate In diethylene glycol dimethyl ether at 140℃; for 2h; Microwave irradiation;	160 mg

(R)-4-hydroxy-2-pyrrolidinone (22677-21-0) + p-toluenesulfonyl chloride (98-59-9) → C11H13NO4S

Conditions	Yield
With dmap In dichloromethane at 0 - 20℃; for 16h;

(R)-4-hydroxy-2-pyrrolidinone (22677-21-0) + di-tert-butyl dicarbonate (24424-99-5) + tert-butyldimethylsilyl chloride (18162-48-6) → C15H31NO4Si

Conditions	Yield
Stage #1: (R)-4-hydroxy-2-pyrrolidinone; di-tert-butyl dicarbonate Stage #2: tert-butyldimethylsilyl chloride With lithium triethylborohydride

Upstream product

• 208103-39-3 3(R)-hydroxy-4-aminobutyric acid ethyl ester 
• 135056-42-7 1-(1'-phenylethyl)-4-phenylmethoxypyrrolidin-2-one 
• 131653-48-0 (4R)-4-hydroxy-1-<(1S)-1-phenylethyl>pyrrolidin-2-one 
• 10488-69-4 ethyl (L)-4-chloro-3-hydroxybutyrate 
• 75-77-4 chloro-trimethyl-silane 
• 924-49-2 DL-4-amino-3-hydroxybutyric acid 
• 999-97-3 1,1,1,3,3,3-hexamethyl-disilazane 
• 119494-27-8 ethyl 4-azido-3-hydroxybutanoate 
• 10488-68-3 methyl 4-chloro-3-hydroxybutanoate 
• 108-10-1 4-methyl-2-pentanone 
• 86728-85-0 ethyl 4-chloro-3-hydroxybutanoate 
• 68252-20-0 4-Trimethylsilyloxy-1H-pyrrolidin-2one 

Downstream Products

• 945635-00-7 (R)-4-[tert-butyl(diphenyl)silanyloxy]pyrrolidin-2-one 
• 108309-77-9 4-benzoylthio-2-pyrrolidone 
• 1253926-33-8 (R)-1-(4-bromo-3-methyl-phenyl)-4-hydroxy-pyrrolidin-2-one 
• 1362910-95-9 (R)-1-(2-(difluoro(4-fluorophenyl)methyl)-4-(methylthio)quinazolin-7-yl)-4-hydroxypyrrolidin-2-one 
• 97899-28-0 2-Pyrrolidon-4-yl p-Toluenesulfonate 
• 914104-03-3 tert-butyl [2-(4-{[(4R)-4-hydroxy-2-oxopyrrolidin-1-yl]methyl}phenyl)ethyl]carbamate 
• 80269-80-3 4-benzoyloxy-2-pyrrolidinone 
• 64097-45-6 4-acetoxy-2-pyrrolidinone 
• 7013-07-2 (R)-4-Amino-3-hydroxybutanoic acid 

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