42831-50-5

Basic information

• Product Name: 5-Methyl-4-isoxazolecarboxylic acid
• Synonyms: TIMTEC-BB SBB005909;5-METHYLISOXAZOLE-4-CARBOXYLIC ACID;5-METHYL-4-ISOXASOLECARBOXYLIC ACID;5-METHYL-4-ISOXAZOLECARBOXYLIC ACID;5-Methyl-4-Isooxazolecarboxylic Acid;5-METHYLISOXAZOLE-4-CARBOXYLIC;5-MethylIsoxazole-4-CarboxalicAcid,Leflunomide;4-Isoxazolecarboxylic acid,5-Methyl
• CAS NO: 42831-50-5
• Molecular Formula: C₅H₅NO₃
• Molecular Weight: 127.1
• EINECS: 1312995-182-4
• Product Categories: Acids and Derivatives;Heterocycles;Isoxazoles, Oxadiazoles, Oxazoles;Carboxylic Acids;Oxazoles, Isoxazoles & Benzoxazoles;Oxazole&Isoxazole;Organic acids;(intermediate of leflunomide);Heterocyclic Compounds;Carboxylic Acids;Oxazoles, Isoxazoles & Benzoxazoles;Building Blocks;Heterocyclic Building Blocks;Isoxazoles;Intermediates;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 42831-50-5.mol
• Article Data: 11

Chemical Properties

• Melting Point: 144-148 °C(lit.)
• Boiling Point: 308.3 °C at 760 mmHg
• Flash Point: 140.3 °C
• Appearance: cream to brown solid
• Density: 1.348 g/cm³
• Vapor Pressure: 0.000297mmHg at 25°C
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 2.85±0.25(Predicted)
• BRN: 116000
• CAS DataBase Reference: 5-Methyl-4-isoxazolecarboxylic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 5-Methyl-4-isoxazolecarboxylic acid(42831-50-5)
• EPA Substance Registry System: 5-Methyl-4-isoxazolecarboxylic acid(42831-50-5)

Safety Data

• Hazard Codes: Xi,F
• Statements: 36/37/38-37/38-36-10
• Safety Statements: 22-26-36/37/39-36-16
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 42831-50-5(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 42831-50-5 differently. You can refer to the following data:
1. An intermediate for synthesis of Leflunomide (L322750). Herbicidal activities towards Digitaria ciliaris
2. 5-Methylisoxazole-4-carboxylic Acid (Leflunomide EP Impurity D) is an intermediate for synthesis of Leflunomide (L322750). Herbicidal activities towards Digitaria ciliaris.

Flammability and Explosibility

Nonflammable

InChI:InChI=1/C5H5NO3/c1-3-4(5(7)8)2-6-9-3/h2H,1H3,(H,7,8)/p-1

Upstream product

• 33142-24-4 2-formyl-3-oxo-butyric acid ethyl ester 
• 134653-70-6 ethyl 2-[(dimethylamino)methylene]-3-oxobutanoate 
• 100367-49-5 (5-methylisoxazol-4-yl)methanol 
• 51135-73-0 5-methylisoxazole-4-carboxylic acid ethyl ester 
• 3788-94-1 2-ethoxymethylene-3-oxobutanoic acid ethyl ester 

Downstream Products

• 67305-24-2 5-methylisoxazole-4-carbonyl chloride 
• 210627-03-5 N-(4-aminophenyl)-5-methylisoxazole-4-carboxamide 
• 1431385-47-5 N-{3-fluoro-4-[1-methyl-3-(trifluoromethyl)pyrazol-5-yl]phenyl}(5-methylisoxazol-4-yl)carboxamide 

Relevant articles and documents

Microchannel continuous preparation method of 5-methylisoxazole-4-formic acid

The invention relates to the field of organic synthesis, and in particular relates to a microchannel continuous preparation method of 5-methylisoxazole-4-formic acid, and the method comprises the following steps: dissolving 2-ethoxymethylacetoacetate in a polar organic solvent to obtain a solution A, dissolving hydroxylamine hydrochloride and an organic base in the polar organic solvent to obtaina solution B; respectively pumping the solution A and the solution B into a microchannel reactor simultaneously for reaction; after the reaction is completed, collecting the reaction liquid flowing out of the microchannel reactor, decompressing and desolventizing, adding sulfuric acid for heating hydrolysis, and performing recrystallization to obtain the 5-methyl isoxazole-4-formic acid. The method has high purity of the reaction process system, reduces the purification loss of products, enables the yield of the two-step reaction to reach more than 95%, reduces material consumption, saves cost, and provides high-quality raw materials for the production of leflunomide.

Synthesis and in vivo antifibrotic activity of novel leflunomide analogues

Novel Leflunomide analogues were synthesized and evaluated in vivo against thioacetamide (TAA) induced liver fibrosis in rats. All the animals which were treated with the new analogues showed improved or comparable survival rates to those treated with Leflunomide. Animals which were treated with compounds 8d, 8e, 9 and 11 have shown improved liver parameters than Leflunomide treated animals. Histopathology of the liver has shown that compound 8a is the most active compound, which decreases fibrosis to a minimal level and compounds 8c, 8e and 11 are active compounds with fibrosis score 2-3 which is better than that of Leflunomide.

AN IMPROVED PROCESS FOR PREPARATION OF LEFLUNOMIDE

This invention describes a process for the preparation of N-(4-trifluoromethyl)-5-methylisoxazole-4-carboxamide commonly known as leflunomide comprising : (a) reacting ethylaceto acetate, triethylorthoformate, and acetic anhydride with simultaneous distillation to form ethyl ethoxymethyleneacetoacetic ester; (b) reacting the ethyl ethoxymethyleneacetoacetic ester with aqueous hydroxylamine without using any external base and without any distillation to form ethyl-5-methylisoxazole-4-carboxylate; (c) reacting the ethyl-5-methylisoxazole-4-carboxylate with strong acid to form -5-methylisoxazole-4-carboxylic acid; (d) 5-methylisoxazole-4-carboxylic acid is reacted with thionyl chloride in presence of N, N-Dimethylformamide and equimolar of 4-trifluoromethylaniline without any external base to obtain highly pure Leflunomide.