3919-74-2

Basic information

• Product Name: 3-(2-Chloro-6-fluorophenyl)-5-methylisoxazole-4-carboxylic acid
• Synonyms: 3-(2-Chloro-6-fluorophenyl)-5-methylisoxazole-4-carbonitrile-4-carboxylicacid;3-(2-Chloro-6-fluorophenyl)-5-methylisoxazole-4-carboxylic acid 97%;3-(2-Chloro-6-fluorophenyl)-5-methylisoxazole-4-carboxylicacid97%;3-(2-CHLORO-6-FLUOROPHENYL)-5-METHYLISOXAZOLE-4-CARBOXYLIC A;3-(2-Chloro-6-fluorophenyl)-5-methyl-4-isoxazolecarboxic Acid;3-(2-CHLORO-6-FLUOROPHENYL)-5-METHYLISOXAZOLE-4-CARBOXYLIC ACID;LABOTEST-BB LT00454096;RARECHEM AL BO 0550
• CAS NO: 3919-74-2
• Molecular Formula: C₁₁H₇ClFNO₃
• Molecular Weight: 255.63
• EINECS: 223-486-8
• Product Categories: Oxazole&Isoxazole
• Mol File: 3919-74-2.mol
• Article Data: 9

Chemical Properties

• Melting Point: 202 °C
• Boiling Point: 360.7 °C at 760 mmHg
• Flash Point: 171.9 °C
• Appearance: /
• Density: 1.454 g/cm³
• Vapor Pressure: 0.00046mmHg at 25°C
• Refractive Index: 1.533
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: Chloroform (Slightly, Heated), Methanol (Very Slightly)
• PKA: 2.13±0.25(Predicted)
• BRN: 806523
• CAS DataBase Reference: 3-(2-Chloro-6-fluorophenyl)-5-methylisoxazole-4-carboxylic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 3-(2-Chloro-6-fluorophenyl)-5-methylisoxazole-4-carboxylic acid(3919-74-2)
• EPA Substance Registry System: 3-(2-Chloro-6-fluorophenyl)-5-methylisoxazole-4-carboxylic acid(3919-74-2)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38-37/38-36
• Safety Statements: 26-36/37/39-37/39-36
• Hazardous Substances Data: 3919-74-2(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 3919-74-2 differently. You can refer to the following data:
1. 3-(2-Chloro-6-fluorophenyl)-5-methylisoxazole-4-carboxylic Acid is an impurity of Flucloxacillin (F419200), a new semisynthetic penicillin
2. 3-(2-Chloro-6-fluorophenyl)-5-methylisoxazole-4-carboxylic Acid (Flucloxacillin EP Impurity D) is an impurity of Flucloxacillin (F419200), a new semisynthetic penicillin with broad spectrum of antibacterial activity.

InChI:InChI=1/C8H6FNO4/c1-14-8(11)6-3-2-5(10(12)13)4-7(6)9/h2-4H,1H3

Synthetic route

(3-(2-chloro-6-fluorophenyl)-5-methylisoxazol-4-yl)methanol (1239346-71-4) → 3-(2-chloro-6-flourophenyl)-5-methyl-isoxazole-4-carboxylic acid (3919-74-2)

Conditions	Yield
Stage #1: (3-(2-chloro-6-fluorophenyl)-5-methylisoxazol-4-yl)methanol With potassium permanganate; disodium hydrogenphosphate In methanol; water at 25℃; Continuous flow conditions; Sonication; Stage #2: With hydrogenchloride; sodium thiosulfate; sodium chloride In methanol; water; ethyl acetate	87%

2-chloro-6-fluoro-N-hydroxybenzene-1-carbonimidoyl chloride (51088-25-6) + acetoacetic acid methyl ester (105-45-3) → 3-(2-chloro-6-flourophenyl)-5-methyl-isoxazole-4-carboxylic acid (3919-74-2)

Conditions	Yield
With ethanol; triethylamine at 5℃;	72%

methyl 3-(2-chloro-6-fluorophenyl)-5-methylisoxazole-4-carboxylate (4415-09-2) → 3-(2-chloro-6-flourophenyl)-5-methyl-isoxazole-4-carboxylic acid (3919-74-2)

Conditions	Yield
With potassium hydroxide In ethanol
With water; sodium hydroxide In methanol for 1h; pH=11 - 13; Reflux;
With water; sodium hydroxide In ethanol at 60℃; for 24h;
With sodium hydroxide In water for 3h;

2-chloro-6-fluorobenzaldehyde (387-45-1) → 3-(2-chloro-6-flourophenyl)-5-methyl-isoxazole-4-carboxylic acid (3919-74-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: (i) NH2OH, (ii) Cl2, CHCl3, (iii) /BRN= 506727/, MeOH 2: aq. KOH / ethanol View Scheme
Multi-step reaction with 4 steps 1.1: hydroxylamine sulfate / methanol / 0.5 h 1.2: 0.5 h / pH 8 - 9 / Reflux 2.1: chlorine / methanol / 0 - 5 °C 3.1: sodium hydroxide / methanol / 0.5 h / 0 - 5 °C / pH 10 3.2: 2 h / 0 - 20 °C / pH 9 4.1: water; sodium hydroxide / methanol / 1 h / pH 11 - 13 / Reflux View Scheme
Multi-step reaction with 3 steps 1: sodium carbonate; hydroxylamine hydrochloride / ethanol; water / 2 h / 20 °C 2: pyridine; N-chloro-succinimide / chloroform / 1.5 h / 20 °C 3: ethanol; triethylamine / 5 °C View Scheme

2-chloro-6-fluoro-N-hydroxybenzene-1-carbonimidoyl chloride (51088-25-6) → 3-(2-chloro-6-flourophenyl)-5-methyl-isoxazole-4-carboxylic acid (3919-74-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium hydroxide / methanol / 0.5 h / 0 - 5 °C / pH 10 1.2: 2 h / 0 - 20 °C / pH 9 2.1: water; sodium hydroxide / methanol / 1 h / pH 11 - 13 / Reflux View Scheme

N-[(2-chloro-6-fluorophenyl)methylidene]hydroxylamine (443-33-4) → 3-(2-chloro-6-flourophenyl)-5-methyl-isoxazole-4-carboxylic acid (3919-74-2)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: chlorine / methanol / 0 - 5 °C 2.1: sodium hydroxide / methanol / 0.5 h / 0 - 5 °C / pH 10 2.2: 2 h / 0 - 20 °C / pH 9 3.1: water; sodium hydroxide / methanol / 1 h / pH 11 - 13 / Reflux View Scheme
Multi-step reaction with 2 steps 1: pyridine; N-chloro-succinimide / chloroform / 1.5 h / 20 °C 2: ethanol; triethylamine / 5 °C View Scheme

2-chloro-6-fluorobenzaldehyde (387-45-1) + acetoacetic acid methyl ester (105-45-3) → 3-(2-chloro-6-flourophenyl)-5-methyl-isoxazole-4-carboxylic acid (3919-74-2)

Conditions	Yield
Stage #1: 2-chloro-6-fluorobenzaldehyde With hydroxylamine sulfate In methanol at 20 - 40℃; for 1h; Stage #2: With chlorine; sodium carbonate; triethylamine In methanol at 0 - 20℃; for 24h; pH=~ 9.5; Inert atmosphere; Stage #3: acetoacetic acid methyl ester With sodium carbonate In methanol pH=~ 7 - 7.5;

ethyl 3-(2-chloro-6-fluorophenyl)-5-methylisoxazole-4-carboxylate (83817-51-0) → 3-(2-chloro-6-flourophenyl)-5-methyl-isoxazole-4-carboxylic acid (3919-74-2)

Conditions	Yield
With water; sodium hydroxide In ethanol at 60℃; for 24h;

floxacillin (5250-39-5, 24223-74-3) → carbon dioxide (124-38-9) + 5,5-dimethyl-thiazolidine-2,4-dicarboxlic acid + 3-(2-chloro-6-flourophenyl)-5-methyl-isoxazole-4-carboxylic acid (3919-74-2)

Conditions	Yield
With potassium tellurite; sulfuric acid at 14.84℃; Kinetics; Thermodynamic data; Temperature;

3-(2-chloro-6-flourophenyl)-5-methyl-isoxazole-4-carboxylic acid (3919-74-2) → 3-(2-chloro-6-fluorophenyl)-5-methylisoxazole-4-carbonyl chloride

Conditions	Yield
With phosphorus pentachloride at 45℃; for 1h;	88%
With phosphorus pentachloride In toluene
With phosphorus pentachloride In toluene

3-(2-chloro-6-flourophenyl)-5-methyl-isoxazole-4-carboxylic acid (3919-74-2) → 3-(2-chloro-6-fluorophenyl)-5-methylisoxazole-4-carboxamide (4415-11-6)

Conditions	Yield
(i) SOCl2, (ii) NH3, acetone; Multistep reaction;
Multi-step reaction with 2 steps 1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 1 h / Reflux 2: sodium carbonate; ammonium hydroxide / water; diethyl ether / 3.17 h / 0 - 25 °C View Scheme

(2-chloro-6-fluorophenyl)methanol (56456-50-9) + 3-(2-chloro-6-flourophenyl)-5-methyl-isoxazole-4-carboxylic acid (3919-74-2) → (2-chloro-6-fluoro-phenyl)methyl N-(3-(2-chloro-6-fluoro-phenyl)-5-methyl-1,2-oxazol-4-yl)carbamate (1104461-35-9)

Conditions	Yield
With diphenyl phosphoryl azide; triethylamine In 1,4-dioxane Heating;

3-(2-chloro-6-flourophenyl)-5-methyl-isoxazole-4-carboxylic acid (3919-74-2) → Prop-2-ynyl 3-(2-chloro-6-fluorophenyl)-5-methylisoxazole-4-carboxylate (1391026-03-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: phosphorus pentachloride / 1 h / 45 °C 2: triethylamine / dichloromethane / 2 h / 0 - 20 °C View Scheme

3-(2-chloro-6-flourophenyl)-5-methyl-isoxazole-4-carboxylic acid (3919-74-2) → (1-(2-morpholino-2-oxoethyl)-1H-1,2,3-triazol-4-yl)methyl 3-(2-chloro-6-fluorophenyl)-5-methylisoxazole-4-caroboxylate (1391026-19-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: phosphorus pentachloride / 1 h / 45 °C 2: triethylamine / dichloromethane / 2 h / 0 - 20 °C 3: copper(ll) sulfate pentahydrate; sodium L-ascorbate / water; tert-butyl alcohol / 20 °C View Scheme

3-(2-chloro-6-flourophenyl)-5-methyl-isoxazole-4-carboxylic acid (3919-74-2) → (1-benzyl-1H-1,2,3-triazol-4-yl)methyl 3-(2-chloro-6-fluorophenyl)-5-methylisoxazole-4-carboxylate (1391026-20-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: phosphorus pentachloride / 1 h / 45 °C 2: triethylamine / dichloromethane / 2 h / 0 - 20 °C 3: copper(ll) sulfate pentahydrate; sodium L-ascorbate / water; tert-butyl alcohol / 20 °C View Scheme

3-(2-chloro-6-flourophenyl)-5-methyl-isoxazole-4-carboxylic acid (3919-74-2) → (1-(4-(1,3-dioxoisoindolin-2-yl)butyl)-1H-1,2,3-triazol-4-yl)methyl 3-(2-chloro-6-fluorophenyl)-5-methylisoxazole-4-carboxylate (1391026-21-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: phosphorus pentachloride / 1 h / 45 °C 2: triethylamine / dichloromethane / 2 h / 0 - 20 °C 3: copper(ll) sulfate pentahydrate; sodium L-ascorbate / water; tert-butyl alcohol / 20 °C View Scheme

3-(2-chloro-6-flourophenyl)-5-methyl-isoxazole-4-carboxylic acid (3919-74-2) → (1-butyl-1H-1,2,3-triazol-4yl)methyl 3-(2-chloro-6-fluorophenyl)-5-methylisoxazole-4-carboxylate (1391026-22-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: phosphorus pentachloride / 1 h / 45 °C 2: triethylamine / dichloromethane / 2 h / 0 - 20 °C 3: copper(ll) sulfate pentahydrate; sodium L-ascorbate / water; tert-butyl alcohol / 20 °C View Scheme

3-(2-chloro-6-flourophenyl)-5-methyl-isoxazole-4-carboxylic acid (3919-74-2) → (1-allyl-1H-1,2,3-triazol-4-yl)methyl 3-(2-chloro-6-fluorophenyl)-5-methylisoxazole-4 carboxylate (1391026-23-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: phosphorus pentachloride / 1 h / 45 °C 2: triethylamine / dichloromethane / 2 h / 0 - 20 °C 3: copper(ll) sulfate pentahydrate; sodium L-ascorbate / water; tert-butyl alcohol / 20 °C View Scheme

3-(2-chloro-6-flourophenyl)-5-methyl-isoxazole-4-carboxylic acid (3919-74-2) → flushloxilin triethylamine

Conditions	Yield
Multi-step reaction with 2 steps 1.1: triethylamine / dichloromethane / 0.67 h / -5 - 0 °C 2.1: 30 - 35 °C 2.2: 1 h / -5 - 0 °C View Scheme

3-(2-chloro-6-flourophenyl)-5-methyl-isoxazole-4-carboxylic acid (3919-74-2) → Flucloxacillin sodium (1847-24-1)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: triethylamine / dichloromethane / 0.67 h / -5 - 0 °C 2.1: 30 - 35 °C 2.2: 1 h / -5 - 0 °C 3.1: sodium isooctanoate / acetone; water; ethyl acetate / 3 h / 20 - 25 °C View Scheme

pivaloyl chloride (3282-30-2) + 3-(2-chloro-6-flourophenyl)-5-methyl-isoxazole-4-carboxylic acid (3919-74-2) → C16H15ClFNO4

Conditions	Yield
With triethylamine In dichloromethane at -5 - 0℃; for 0.666667h; Time;

di(benzothiazol-2-yl)disulfide (120-78-5) + 3-(2-chloro-6-flourophenyl)-5-methyl-isoxazole-4-carboxylic acid (3919-74-2) → C18H10ClFN2O2S2

Conditions	Yield
With triethylamine; triethyl phosphite In dichloromethane at 5 - 15℃; Large scale;

3-(2-chloro-6-flourophenyl)-5-methyl-isoxazole-4-carboxylic acid (3919-74-2) → 3-(2-chloro-6-fluorophenyl)-5-methylisoxazole-4-carbothioamide

Conditions	Yield
Multi-step reaction with 3 steps 1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 1 h / Reflux 2: sodium carbonate; ammonium hydroxide / water; diethyl ether / 3.17 h / 0 - 25 °C 3: Lawessons reagent / 1,4-dioxane / 4 h / Reflux View Scheme

3-(2-chloro-6-flourophenyl)-5-methyl-isoxazole-4-carboxylic acid (3919-74-2) → 3-(2-chloro-6-fluorophenyl)-5-methyl-4-(thiazol-2-yl)isoxazole

Conditions	Yield
Multi-step reaction with 4 steps 1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 1 h / Reflux 2: sodium carbonate; ammonium hydroxide / water; diethyl ether / 3.17 h / 0 - 25 °C 3: Lawessons reagent / 1,4-dioxane / 4 h / Reflux 4: water / 24 h / Reflux View Scheme

3-(2-chloro-6-flourophenyl)-5-methyl-isoxazole-4-carboxylic acid (3919-74-2) → C11H9ClFN3O2

Conditions	Yield
Stage #1: 3-(2-chloro-6-flourophenyl)-5-methyl-isoxazole-4-carboxylic acid With thionyl chloride for 3h; Reflux; Stage #2: With hydrazine hydrate In 1,4-dioxane at 25℃; for 2h;

3-(2-chloro-6-flourophenyl)-5-methyl-isoxazole-4-carboxylic acid (3919-74-2) → 2-[3-(2-chloro-6-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]-5-methyl-1,3,4-oxadiazole

Conditions	Yield
Multi-step reaction with 2 steps 1.1: thionyl chloride / 3 h / Reflux 1.2: 2 h / 25 °C 2.1: 6 h / 140 °C / Microwave irradiation View Scheme

thiazolidine-2-one (2682-49-7) + 3-(2-chloro-6-flourophenyl)-5-methyl-isoxazole-4-carboxylic acid (3919-74-2) → C14H10ClFN2O3S

Conditions	Yield
Stage #1: 3-(2-chloro-6-flourophenyl)-5-methyl-isoxazole-4-carboxylic acid With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 0.333333h; Stage #2: thiazolidine-2-one In dichloromethane at 20℃;

3-(2-chloro-6-flourophenyl)-5-methyl-isoxazole-4-carboxylic acid (3919-74-2) → C19H14ClFN2O3

Conditions	Yield
Multi-step reaction with 2 steps 1: thionyl chloride; N,N-dimethyl-formamide / dichloromethane / 40 °C 2: potassium carbonate / toluene / 0.42 h / 40 °C / Microwave irradiation View Scheme

3-(2-chloro-6-flourophenyl)-5-methyl-isoxazole-4-carboxylic acid (3919-74-2) → C20H16ClFN2O3

Conditions	Yield
Multi-step reaction with 2 steps 1: thionyl chloride; N,N-dimethyl-formamide / dichloromethane / 40 °C 2: potassium carbonate / toluene / 0.42 h / 40 °C / Microwave irradiation View Scheme

Upstream product

• 1239346-71-4 (3-(2-chloro-6-fluorophenyl)-5-methylisoxazol-4-yl)methanol 
• 51088-25-6 2-chloro-6-fluoro-N-hydroxybenzene-1-carbonimidoyl chloride 
• 105-45-3 acetoacetic acid methyl ester 
• 5250-39-5 floxacillin 
• 83817-51-0 ethyl 3-(2-chloro-6-fluorophenyl)-5-methylisoxazole-4-carboxylate 
• 387-45-1 2-chloro-6-fluorobenzaldehyde 
• 443-33-4 N-[(2-chloro-6-fluorophenyl)methylidene]hydroxylamine 
• 4415-09-2 methyl 3-(2-chloro-6-fluorophenyl)-5-methylisoxazole-4-carboxylate 

Downstream Products

• 4415-11-6 3-(2-chloro-6-fluorophenyl)-5-methylisoxazole-4-carboxamide 
• 1391026-19-9 (1-(2-morpholino-2-oxoethyl)-1H-1,2,3-triazol-4-yl)methyl 3-(2-chloro-6-fluorophenyl)-5-methylisoxazole-4-caroboxylate 
• 1391026-20-2 (1-benzyl-1H-1,2,3-triazol-4-yl)methyl 3-(2-chloro-6-fluorophenyl)-5-methylisoxazole-4-carboxylate 
• 1391026-21-3 (1-(4-(1,3-dioxoisoindolin-2-yl)butyl)-1H-1,2,3-triazol-4-yl)methyl 3-(2-chloro-6-fluorophenyl)-5-methylisoxazole-4-carboxylate 
• 1391026-22-4 (1-butyl-1H-1,2,3-triazol-4yl)methyl 3-(2-chloro-6-fluorophenyl)-5-methylisoxazole-4-carboxylate 
• 1391026-23-5 (1-allyl-1H-1,2,3-triazol-4-yl)methyl 3-(2-chloro-6-fluorophenyl)-5-methylisoxazole-4 carboxylate 
• 69399-79-7 3-(2-chloro-6-fluorophenyl)-5-methylisoxazole-4-carbonyl chloride 
• 175204-42-9 3-(2-chloro-6-fluorophenyl)-5-methylisoxazole-4-carbothioamide 
• 1847-24-1 Flucloxacillin sodium 
• 1104461-35-9 (2-chloro-6-fluoro-phenyl)methyl N-(3-(2-chloro-6-fluoro-phenyl)-5-methyl-1,2-oxazol-4-yl)carbamate 

Relevant articles and documents

Synthesis, Crystal Structure, and Herbicidal Activity of 3-(2-Chloro-6-fuorophenyl)-4-(2-oxooxazolidine-3-carbonyl)-5-methylisoxazole

ABSTRACT A novel N-aroyl diketone derivative, 3-(2-chloro-6-fluorophenyl)-4-(2-oxooxazolidine-3-carbonyl)-5-methylisoxazole (C14H10ClFN2O4, Mr=324.69), was designed via fragment analysis and coupling strategy that led to highly potent and bio-selective herbicide. The title compound was prepared by a multistep-reaction, including nucleophilic addition and N-acylation reaction using 2-chloro-6-fluorobenzaldehyde as the starting materials in 83.4% yield. The product was characterized by infrared, proton nuclear magnetic resonance, Carbon-13 nuclear magnetic resonance, human resource management system, and X-ray diffraction. The title compound crystallized in the monoclinic system, space group P21/n with a=10.7119(4) ?, b=17.5875(7) ?, c=11.5151(7) ?, b=100.927(2)°, Z=8, V=2870.0(2) ?3, F(000)=1328, Dc=1.503 Mg/m3, crystal size: 0.130 × 0.120 ×0.100 mm. The herbicidal activity was tested against the gramineous weed Echinochloa crus-galli and broadleaf Abutilon juncea.

1-(4-(ISOXAZOL-5-YL)-1H-PYRAZOL-1-YL)-2-METHYLPROPAN-2-OL DERIVATIVES AND RELATED COMPOUNDS AS IL-17 AND IFN-GAMMA INHIBITORS FOR TREATING AUTOIMMUNE DISEASES AND CHRONIC INFLAMMATION

The present invention relates to compounds of the general formula (I), and the pharmaceutically acceptable salts and solvates thereof, wherein Ar, Z and Y are as described herein and R1 is a group of the structure (formula (II)), wherein n is 0 or 1; R2 is H, deuterium or methyl; R3 is methyl, trilluoromethyl, ethyl, or taken with R2 together forms a cyclopropyl group, or R3 forms a methylene bridge to the carbon atom marked *, which are suitable for the treatment of autoimmune diseases and chronic inflammation.

NOVEL PIPERAZINE ANALOGS WITH SUBSTITUTED HETEROARYL GROUPS AS BROAD-SPECTRUM INFLUENZA ANTIVIRALS

A compound of the following Formula (I) is set forth, including pharmaceutically acceptable salts thereof: wherein Het is a 5 or 6-membered heterocycle with -N, -O, or -S adjacent to the -Ar substituent or adjacent to the point of attachment for the -Ar substituent; Ar is aryl or heteroaryl; R is -CH3, -CH2F, -CHF2 or -CH=CH2; V is -H, -CH3 or =0; W is -NO2, -CI, -Br, -CH2OH, or -CN; X is -CI, -Br, -F, -CH3, -OCH3, or -CN; Y is -CH or -N; and Z is -CH or -N. This compound is useful in compositions for the prevention and treatment of influenza virus.