68108-18-9

Basic information

• Product Name: (S)-4-Hydroxy-2-pyrrolidinone
• Synonyms: 2-PYRROLIDINONE, 4-HYDROXY-, (S);2-PYRROLIDINONE, 4-HYDROXY-, (4S)-;(4S)-4-HYDROXYPYRROLIDIN-2-ONE;4-HYDROXY-PYRROLIDIN-2-ONE;(S)-(-)-4-HYDROXY-2-PYRROLIDINONE;(S)-(+)-4-HYDROXY-2-PYRROLIDINONE;(S)-4-HYDROXY-2-PYRROLIDINONE;(S)-4-HYDROXY-2-PYRROLIDONE
• CAS NO: 68108-18-9
• Molecular Formula: C₄H₇NO₂
• Molecular Weight: 101.1
• Product Categories: Pyrrolidinone derivatives;Drug Intermediates;Chiral;Amines;Chiral Reagents;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 68108-18-9.mol

Chemical Properties

• Melting Point: 156-160 °C
• Boiling Point: 363.6 °C at 760 mmHg
• Flash Point: 173.7 °C
• Appearance: White to off-white/Solid
• Density: 1.292 g/cm³
• Vapor Pressure: 9.26E-07mmHg at 25°C
• Refractive Index: 1.513
• Storage Temp.: Keep in dark place,Sealed in dry,Room Temperature
• PKA: 13.62±0.20(Predicted)
• Water Solubility: Slightly soluble in water
• BRN: 1524192
• CAS DataBase Reference: (S)-4-Hydroxy-2-pyrrolidinone(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-4-Hydroxy-2-pyrrolidinone(68108-18-9)
• EPA Substance Registry System: (S)-4-Hydroxy-2-pyrrolidinone(68108-18-9)

Safety Data

• Hazard Codes: Xn
• Statements: 22-41
• Safety Statements: 22-24/25-36-26
• WGK Germany: 3
• Hazardous Substances Data: 68108-18-9(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(S)-4-Hydroxy-2-pyrrolidinone is used as a starting material for the preparation of biologically significant pyrrolo[1,2:1′,2′]azepino[5,6-b]indole derivatives and substituted azepanes. It is utilized in the pharmaceutical industry for the synthesis of various compounds with potential therapeutic applications.
Used in the Synthesis of Oxiracetam:
(S)-4-Hydroxy-2-pyrrolidinone is used as an (S)-enantiomer intermediate in the preparation of Oxiracetam, a nootropic drug with cognitive-enhancing properties.
Used in Chemical Synthesis:
(S)-4-Hydroxy-2-pyrrolidinone is used as a key intermediate in the synthesis of various γ-amino acids and substituted 2-pyrrolidinones, which are important in the development of new chemical compounds with potential applications in various industries, including pharmaceuticals, agrochemicals, and materials science.

InChI:InChI=1/C4H7NO2/c6-3-1-4(7)5-2-3/h3,6H,1-2H2,(H,5,7)/t3-/m0/s1

Upstream product

• 924-49-2 DL-4-amino-3-hydroxybutyric acid 
• 68252-20-0 4-Trimethylsilyloxy-1H-pyrrolidin-2one 
• 86728-85-0 ethyl 4-chloro-3-hydroxybutanoate 
• 10488-68-3 methyl 4-chloro-3-hydroxybutanoate 
• 75-77-4 chloro-trimethyl-silane 
• 999-97-3 1,1,1,3,3,3-hexamethyl-disilazane 
• 7013-05-0 (S)-4-amino-3-hydroxybutanoic acid 
• 186429-12-9 (S)-4-(1-ethoxy)ethoxy-2-oxopyrrolidine 
• 100181-71-3 (R,S)-isobutyl 3,4-epoxybutyrate 
• 191403-66-4 (S)-N-benzyl-4-hydroxy-pyrrolidin-2-one 
• 141629-19-8 (4S)-4-{[tert-butyl(dimethyl)silyl]oxy}pyrrolidin-2-one 
• 130403-84-8 methyl (3S)-3-hydroxy-4-{[(4-methylphenyl)sulfonyl]oxy}butanoate 
• 119494-27-8 ethyl 4-azido-3-hydroxybutanoate 
• 108-10-1 4-methyl-2-pentanone 

Downstream Products

• 108309-77-9 4-benzoylthio-2-pyrrolidone 
• 64097-45-6 4-acetoxy-2-pyrrolidinone 
• 80269-80-3 4-benzoyloxy-2-pyrrolidinone 
• 141629-19-8 (4S)-4-{[tert-butyl(dimethyl)silyl]oxy}pyrrolidin-2-one 
• 142705-97-3 (R)-4-acetylthio-2-oxopyrrolidine 

Relevant articles and documents

Transition-Metal-Free Deconstructive Lactamization of Piperidines

One of the major challenges in organic synthesis is the activation or deconstructive functionalization of unreactive C(sp3)–C(sp3) bonds, which requires using transition or precious metal catalysts. We present here an alternative: the deconstructive lactamization of piperidines without using transition metal catalysts. To this end, we use 3-alkoxyamino-2-piperidones, which were prepared from piperidines through a dual C(sp3)–H oxidation, as transitory intermediates. Experimental and theoretical studies confirm that this unprecedented lactamization occurs in a tandem manner involving an oxidative deamination of 3-alkoxyamino-2-piperidones to 3-keto-2-piperidones, followed by a regioselective Baeyer–Villiger oxidation to give N-carboxyanhydride intermediates, which finally undergo a spontaneous and concerted decarboxylative intramolecular translactamization.

Preparation method of (S)-oxiracetam

The invention discloses a preparation method of (S)-oxiracetam. The preparation method is characterized by comprising the following steps that 1, 2-epoxy ethylacetamide is cyclized in molecules in the presence of a catalyst and alkali to obtain a compound (S)-3-hydroxyl-butyrolactam shown as a formula II; 2, the (S)-3-hydroxyl-butyrolactam obtained in the step 1 reacts with tertiary butyl methyl chlorosilane to obtain a compound protected by the tertiary butyl methyl chlorosilane and shown as a formula III; 3, the compound shown as the formula III performs nucleophilic reaction with bromoacetonitrile under the alkaline condition to obtain a N-cyanomethide shown as a formula IV; 4, the N-cyanomethide shown as the formula IV is subjected to hydrolysis under the acid condition to obtain the (S)-oxiracetam (shown in the description). The method adopts conventional non-achiral raw materials and is low in cost, the (S)-oxiracetam is high in yield, an ee value is high, and a new way is provided for preparation of the (S)-oxiracetam.

Method for preparing intelligence-improving medicine (S)-oxiracetam

The invention discloses a method for preparing an intelligence-improving medicine (S)-oxiracetam. The method comprises the following steps: (1) under the catalysis of 4-dimethylaminopyridine, enabling 2-oxiraneisobutylacetate to contact with ammonia gas to react, so as to obtain (S)-4-hydroxyl-2-oxopyrrolidine; (2) enabling the (S)-4-hydroxyl-2-oxopyrrolidine obtained by the step (1) to react with tert-butyldimethylsilyl chloride, so as to obtain a compound shown as a formula III, which is protected by tert-butyl dimethylsilane; (3) enabling the compound shown as the formula III and 2-bromoacetic ester to be subjected to a nucleophilic reaction under an alkaline condition, so as to obtain a compound shown as a formula IV; (4) under the catalysis of ammonium chloride, enabling the compound shown as the formula IV and ammonia gas to be subjected to an ammonolysis reaction, so as to obtain the (S)-oxiracetam as shown in the description. The (S)-oxiracetam prepared by the method provided by the invention is high in yield, high in ee value and relatively low in cost, and a preparation process is simple and is suitable for industrial production.

Nucleophilic ring-opening of epoxide and aziridine acetates for the stereodivergent synthesis of β-Hydroxy and β-Amino γ-Lactams

A highly regio- and stereoselective synthesis of novel β,γ- disubstituted γ-lactams with either an anti or syn relative configuration was developed from readily available epoxide and aziridine acetates. The key steps include the regio- and diastereocontrolled nucleophilic ring-opening of these three-membered heterocycles followed by mild reductive cyclization of the γ-azido ester intermediate. The method was also extended to an asymmetric synthesis of (4R,5S)-4-hydroxy-5-phenylpyrrolidin-2-one from a chiral epoxide acetate. The main features of this versatile synthesis of functionalized γ-lactams include the involvement of inexpensive reagents and mild conditions together with high chemical efficiency.

PROCESS FOR STRAIGHTENING KERATIN FIBRES WITH A HEATING MEANS AND DENATURING AGENTS

The invention relates to a process for straightening keratin fibres, comprising: (i) a step in which a straightening composition containing at least two denaturing agents is applied to the keratin fibres, (ii) a step in which the temperature of the keratin fibres is raised, using a heating means, to a temperature of between 110 and 250° C.

Simple and efficient cleavage of the N-(1-phenylethyl) unit of carboxamides with methanesulfonic acid

Cleavage of the N-(1-phenylethyl) unit of carboxamides using less than 1 equiv of MsOH in refluxing toluene was found to be simple and very efficient leading to the desired amides in good to excellent yields, and also proved to be more effective compared with reductive methods using hydrogen sources, or acid hydrolysis reagents such as TFA and TsOH. The method selectively cleaved only the N-(1-phenylethyl) group of N-benzyl-N-(1-phenylethyl)amides.

An efficient scalable process for the synthesis of N-Boc-2-tert-butyldimethylsiloxypyrrole

A safe, reliable and scalable process for the preparation of N-Boc-2-tert-butyldimethylsiloxy-pyrrole (TBSOP) is described. In a three-step, one-pot sequence (±)-4-amino-3-hydroxybutyric acid was converted to N-Boc-4-hydroxy-2-pyrrolidinone. This stable crystalline product was isolated by filtration directly from the reaction mixture. Dehydration followed by enolization and silylation produced the target compound without the need for chromatographic purification. The process was demonstrated in the pilot plant to make multikilogram quantities of material in 85% overall yield.

Process for producing optically active alcohol

A novel process in which an optically active alcohol compound having a desired absolute configuration and a high optical purity can be obtained by asymmetrically hydrogenating a β-keto acid compound through a simple operation. An optically active alcohol represented by the following general formula (III) : (wherein R1 represents a C1-C15 alkyl group which may have one or more substituents (selected from halogen atoms, a hydroxyl group, an amino group, amino groups protected by a protective group, amino groups protected by a mineral acid or organic acid, amino groups substituted with one or more C1-C4 lower alkyl groups, a benzyloxy group, C1-C4 lower alkoxy groups, C1-C4 lower alkoxycarbonyl groups, and aryl groups) or an aryl group; and R2 represents a C1-C8 lower alkyl group, or a benzyl group which may have one or more substituents) is obtained by asymmetrically hydrogenating a β-keto ester compound represented by the following general formula (I): (wherein R1 and R2 are the same as defined above) in the presence of at least one ruthenium complex having as a ligand an optically active tertiary diphosphine compound represented by the following general formula (II): (wherein R3 and R4 each independently represent a cycloalkyl group, an unsubstituted or substituted phenyl group, or a five-membered heteroaromatic ring residue).

Method of producing 4-hydroxy-2-pyrrolidinone and method of purifying the same

4-Hydroxy-2-pyrrolidinone which is useful as a raw material of drugs can be produced rapidly and highly selectively in a high yield from an optically active or recemic 4-amino-3-hydroxybutylic acid derivative or a 4-azido-3-hydroxybutyric acid derivative by adding a base catalyst to the reaction system. 4-Hydroxy-2-pyrrolidinone having a high optical purity can be obtained by carrying out recrystallization of optically active 4-hydroxy-2-pyrrolidinone without using a poor solvent.

Efficient syntheses of (S)-4-hydroxy-2-pyrrolidinone derivatives

Efficient syntheses of (S)-4-hydroxy-2-pyrrolidinone ((5)-2) and (R)4- acetylthio-2-pyrrolidinone (S), which are key intermediates of oral carbapenem CS-834, were studied. The most efficient route to (S)-2 from (S)- 3-hydroxybutyrolactone (8) was accomplished in high yield via (S)-N-allyl-3- (1-ethoxy)ethoxy-4-hydroxybutyramide (14).