61312-87-6

Basic information

• Product Name: 4-Isobutyl-2-pyrrolidinone
• Synonyms: 2-pyrrolidinone, 4-(2-methylpropyl)-;4-isobutylpyrrolidin-2-one;4-isobutyl-2-pyrrolidinone(SALTDATA: FREE);4-Isobutyl-2-pyrrolidinone (pregabalin lactaM iMpurity);4-(2-Methylpropyl)-;Pregabalin IMpurity IV;Pregabalin LactaM IMpurity;4-ISOBUTYL-2-PYRROLIDIN-1-YLNE
• CAS NO: 61312-87-6
• Molecular Formula: C₈H₁₅NO
• Molecular Weight: 141.21
• Product Categories: Intermediates;Intermediates & Fine Chemicals;Pharmaceuticals;Heterocyclic Compounds;Heterocycles
• Mol File: 61312-87-6.mol

Chemical Properties

• Boiling Point: 269.066°C at 760 mmHg
• Flash Point: 152.254°C
• Appearance: /
• Density: 0.928g/cm³
• Vapor Pressure: 0.007mmHg at 25°C
• Refractive Index: 1.445
• Storage Temp.: Refrigerator
• Solubility: Chloroform (Slightly), Ethyl Acetate (Slightly), Methanol (Slightly)
• PKA: 16.66±0.40(Predicted)
• CAS DataBase Reference: 4-Isobutyl-2-pyrrolidinone(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Isobutyl-2-pyrrolidinone(61312-87-6)
• EPA Substance Registry System: 4-Isobutyl-2-pyrrolidinone(61312-87-6)

Safety Data

• HazardClass: IRRITANT
• Hazardous Substances Data: 61312-87-6(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
4-Isobutyl-2-pyrrolidinone is used as an impurity in the commercial preparation of Pregabalin, a widely prescribed medication for treating neuropathic pain, epilepsy, and generalized anxiety disorder. Its presence in the commercial preparation is essential for the synthesis process.
Used as a Pregabalin Intermediate:
4-Isobutyl-2-pyrrolidinone serves as a crucial intermediate in the synthesis of Pregabalin, playing a significant role in the production of this important medication.
Used in the Production of Pregabalin (P704800):
4-Isobutyl-2-pyrrolidinone is utilized in the manufacturing process of Pregabalin, with the specific product code P704800, ensuring the efficient and effective production of this essential drug.

InChI:InChI=1/C8H15NO/c1-6(2)3-7-4-8(10)9-5-7/h6-7H,3-5H2,1-2H3,(H,9,10)

Upstream product

• 10203-58-4 (2-methylpropyl)-propanedioic acid, diethyl ester 
• 1373869-01-2 t-butyl 4-(2-methylpropyl)-2-oxo-3-pyrrolin-1-carboxylate 
• 1373869-02-3 t-butyl 4-(2-methylpropyl)-2-oxopyrrolidine-1-carboxylate 
• 1373868-93-9 4-methyl-2-methylenepentyl methanesulfonate 
• 1373868-95-1 2-(azidomethyl)-4-methylpent-1-ene 
• 1373868-97-3 N-(4-methyl-2-methylenepentyl)acrylamide 
• 1373869-00-1 t-butyl acryloyl(4-methyl-2-methylenepentyl)carbamate 
• 25044-10-4 2-methylene-4-methyl-pentanoic acid 
• 4361-06-2 isobutylmalonic Acid 
• 87438-94-6 ethyl 2-isobutylacrylate 
• 121505-31-5 4-methyl-2-methylenepentan-1-ol 
• 181289-33-8 (3R)‐3‐(carbamoylmethyl)‐5‐methylhexanoic acid 
• 148553-50-8 pregabilin 
• 53618-21-6 dimethyl 2-(3-methylbutylidene)malonate 

Downstream Products

• 128013-69-4 (R,S)-3-iso-butyl-4-aminobutyric acid 
• 181289-23-6 (S)-4-isobutyl-pyrrolidin-2-one 
• 181289-22-5 (R)-(+)-4-isobutyl-2-pyrrolidinone 
• 148553-50-8 pregabilin 

Relevant articles and documents

Method for preparing 4-isobutyl pyrrolidone by solvent-free method

The invention discloses a method for preparing 4-isobutyl pyrrolidone by a solvent-free method. The method is characterized in that R-type, S-type or racemic 3-(carbamylmethyl)-5-methylhexanoic acid is used as an initial raw material, 3-aminomethyl-5-methylhexanoic acid is prepared through a Hofmann degradation reaction, and an R-type, S-type or racemic 4-isobutyl pyrrolidone product is prepared through a solvent-free reaction. According to the method, currently prepared sodium hypobromite is used for carrying out the Huffman degradation reaction, so that the defects that sodium hypochlorite is easy to decompose and low in reaction activity can be avoided. The generated 3-aminomethyl-5-methylhexanoic acid is subjected to a melting reaction under the solvent-free condition, pulping and purification are carried out, a small amount of oxidation impurities can be removed, meanwhile, the solid form is improved, finally, suction filtration and drying are carried out, and the 4-isobutyl pyrrolidone product with the purity being 98.5% or above is obtained. In the whole reaction process, less solvent is used, the operation is simple and easy, and the method is clean and environment-friendly.

Asymmetric Amination of α-Chiral Aliphatic Aldehydes via Dynamic Kinetic Resolution to Access Stereocomplementary Brivaracetam and Pregabalin Precursors

Over the last decades biocatalysis has emerged as an indispensable and versatile tool for the asymmetric synthesis of active pharmaceutical ingredients (APIs). In this context, especially transaminases (TAs) have been successfully used for the preparation of numerous α-chiral, optically pure amines, serving as important building blocks for APIs. Here we elaborate on the development of transaminases recognizing the α-chiral centre adjacent to an aldehyde moiety with aliphatic residues, opening up concepts for novel synthetic routes to the antiepileptic drugs Brivaracetam and Pregabalin. The transformation proceeded via dynamic kinetic resolution (DKR) based on the bio-induced racemisation of the aldehyde enantiomers, enabling the amination of the racemic substrates with quantitative conversions. Medium, substrate as well as enzyme engineering gave access to both (R)- and (S)-enantiomers of the amine precursors of the stereocomplementary drugs in high optical purity, representing a short route to mentioned APIs. (Figure presented.).

Method for preparing pregabalin intermediate

The invention discloses a method for preparing a pregabalin intermediate 4-isobutyl-2-pyrrolidone. The method comprises the following steps: by taking pyrrolidine-2,4-diketone as a raw material, carrying out a wittig reaction so as to obtain a compound 3, and carrying out a double-bond hydrogenation reaction on the compound 3 so as to obtain a compound 1, thereby obtaining the target product pregabalin intermediate 4-isobutyl-2-pyrrolidone. The method is simple in operation and high in yield and is a process suitable for large-scale industrial production.

PROCESS FOR PRODUCING OPTICALLY ACTIVE 4-NITRO-BUTANOIC ACID ESTER AND PREGABALIN

PROBLEM TO BE SOLVED: To provide a process for producing optically active pregabalin with low number of reaction steps and low cost, as well as to provide a process for producing optically active 4-nitro-butanoic acid ester for use in said process. SOLUTION: Provided is a process for producing optically active 5-methyl-3-nitromethyl-2-alkoxycarbonyl-hexanoic acid alkyl ester by reacting dialkyl malonate and 4-methyl-1-nitro-1-pentene in the presence of a chiral catalyst containing a pyridine bisoxazoline derivative and calcium oxide; and a process for producing pregabalin using the present production process. SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT

STEREOSELECTIVE REDUCTIVE AMINATION OF ALPHA-CHIRAL ALDEHYDES USING OMEGA-TRANSAMINASES FOR THE SYNTHESIS OF PRECURSORS OF PREGABALIN AND BRIVARACETAM

The present invention relates to processes comprising a combined racemization and stereoselective reductive amination step in which an aldehyde compound of formula (I) is contacted with an (R)-selective ω-transaminase or an (S)-selective ω-transaminase to racemize the compound of formula (I) and obtain an amine compound of formula (II). These processes are useful for the preparation of precursors of pharmaceutically active agents such as brivaracetam and pregabalin.

Multisite organic-inorganic hybrid catalysts for the direct sustainable synthesis of GABAergic drugs

Multisite organic-inorganic hybrid catalysts have been prepared and applied in a new general, practical, and sustainable synthetic procedure toward industrially relevant GABA derivatives. The domino sequence is composed of seven chemical transformations which are performed in two one-pot reactions. The method produces both enantiomeric forms of the product in high enantiopurity as well as the racemate in good yields after a single column purification step. This protocol highlights major process intensification, catalyst recyclability, and low waste generation.

METHOD OF PREPARING LACTAM COMPOUND

Provided is a method of preparing pregabalin and its important intermediate lactam compound. This method does not use hydrogen or high pressure equipment. By a convenient process, high purity of product can be obtained from selecting the proper catalyst and reducing agent with normal equipments. This method is convenient, safe and is of high yield, which is suitable for industry manufacture.

A ring-closing metathesis approach for the synthesis of (±)-pregabalin

Efficient utilization of a Mannich-type reaction and the ring-closing metathesis (RCM) approach that leads to a convenient synthesis of 3-(aminomethyl)-5-methylhexanoic acid (pregabalin) is described. Springer-Verlag 2011.

NOVEL PREGABALIN INTERMEDIATES AND PROCESS FOR PREPARING THEM AND PREGABALIN

The present invention provides novel compounds, which are especially useful as intermediates for the preparation of Pregabalin. The invention also relates to process for preparing these intermediates and Pregabalin.

Cumyl: A better N-protecting group of α-diazo acetamides for intramolecular C-H insertion reaction and its application in the synthesis of pregabalin and 3-benzyloxy pyrrolidine

Via intramolecular C-H insertion of N-cumyl α-diazo acetamides, γ-lactams were efficiently synthesized with excellent regioselectivity. A concise route for the preparation of pregabalin (79% overall yield) and 3-benzyloxy pyrrolidine (21% overall yield) were reported.