112344-52-2

Basic information

• Product Name: flobufen
• Synonyms: flobufen;2-Methyl-4-(2',4'-difluoro-4-biphenylyl)-4-oxobutyric acid;4-(2',4'-Difluorobiphenyl-4-yl)-4-oxo-2-methylbutyric acid;VUFB-16066
• CAS NO: 112344-52-2
• Molecular Formula: C₁₇H₁₄F₂O₃
• Molecular Weight: 304.291
• Mol File: 112344-52-2.mol
• Article Data: 2

Chemical Properties

• Boiling Point: 456.5°Cat760mmHg
• Flash Point: 229.9°C
• Appearance: /
• Density: 1.272g/cm³
• CAS DataBase Reference: flobufen(CAS DataBase Reference)
• NIST Chemistry Reference: flobufen(112344-52-2)
• EPA Substance Registry System: flobufen(112344-52-2)

Safety Data

• Hazardous Substances Data: 112344-52-2(Hazardous Substances Data)

Usage

General Description

Flobufen is a nonsteroidal anti-inflammatory drug (NSAID) that is commonly used for its pain-relieving and anti-inflammatory properties. It works by inhibiting the production of prostaglandins, which are chemicals in the body that cause pain and inflammation. Flobufen is often prescribed to treat conditions such as arthritis, menstrual cramps, and other types of pain and inflammation. It is available in various forms including tablets, capsules, and topical gels. Like other NSAIDs, flobufen may have potential side effects including stomach irritation, stomach ulcers, and an increased risk of heart attack or stroke, so it should only be used under the guidance of a healthcare professional and at the recommended dose.

InChI:InChI=1/C17H14F2O3/c1-10(17(21)22)8-16(20)12-4-2-11(3-5-12)14-7-6-13(18)9-15(14)19/h2-7,9-10H,8H2,1H3,(H,21,22)

Synthetic route

4-(2',4'-difluorobiphenyl-4-yl)-2-methylene-4-oxobutanoic acid (161692-81-5) → 4-(2',4'-difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid (112344-52-2)

Conditions	Yield
With hydrogen; palladium on activated charcoal In 1,4-dioxane at 20℃; under 3750.3 Torr;	74%

2,4-difluorobiphenyl (37847-52-2) + 2-methylsuccinic anhydride (4100-80-5) → 4-(2',4'-difluorobiphenyl-4-yl)-3-methyl-4-oxobutanoic acid + 4-(2',4'-difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid (112344-52-2)

Conditions	Yield
With aluminium trichloride In 1,2-dichloro-ethane 1) 10 degC, 4 h, 2) 20 degC, 16 h;	A n/a B 40.2%

2-methylenesuccinic acid (97-65-4) + potassium bromide → 4-(2',4'-difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid (112344-52-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: 92 percent / Ac2O / 4 h / 80 °C 2: 63 percent / AlCl3 / CH2Cl2 / 1.) 10 deg C, 4 h, 2.) 20 deg C, 2 h 3: 74 percent / H2 / Pd/C / dioxane / 20 °C / 3750.3 Torr View Scheme

itaconic acid anhydride (2170-03-8) → 4-(2',4'-difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid (112344-52-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 63 percent / AlCl3 / CH2Cl2 / 1.) 10 deg C, 4 h, 2.) 20 deg C, 2 h 2: 74 percent / H2 / Pd/C / dioxane / 20 °C / 3750.3 Torr View Scheme

(R)-1-phenyl-ethyl-amine (3886-69-9) + 4-(2',4'-difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid (112344-52-2) → 4-(2',4'-Difluoro-biphenyl-4-yl)-2-methyl-4-oxo-butyric acid; compound with (R)-1-phenyl-ethylamine

Conditions	Yield
In diethyl ether; acetone for 1h;	97%

L-lysine (56-87-1) + 4-(2',4'-difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid (112344-52-2) → (+/-)-4-(2',4'-fifluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid L-(+)-lysine salt

Conditions	Yield
In water; dimethyl sulfoxide	95%

2-methyl-propan-1-ol (78-83-1) + 4-(2',4'-difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid (112344-52-2) → 4-(2',4'-Difluoro-biphenyl-4-yl)-2-methyl-4-oxo-butyric acid isobutyl ester

Conditions	Yield
With thionyl chloride 1.) -15 deg C, 30 min, 2.) 40-45 deg C, 2 h;	91%

4-(2',4'-difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid (112344-52-2) → 4-(2',4'-difluorobipenyl-4-yl)-2-methylbutyric acid (847475-35-8)

Conditions	Yield
With hydrogen; palladium on activated charcoal In water; acetic acid at 60℃; for 5h;	87%

4-(2',4'-difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid (112344-52-2) + cyclohexylamine (108-91-8) → 4-(2',4'-Difluoro-biphenyl-4-yl)-2-methyl-4-oxo-butyric acid; compound with cyclohexylamine

Conditions	Yield
In diethyl ether; acetone for 1h;	86%

4-(2',4'-difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid (112344-52-2) + benzylamine (100-46-9) → 4-(2',4'-Difluoro-biphenyl-4-yl)-2-methyl-4-oxo-butyric acid; compound with benzylamine

Conditions	Yield
In water; dimethyl sulfoxide	72%

ethanol (64-17-5) + 4-(2',4'-difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid (112344-52-2) → 4-(2',4'-Difluoro-biphenyl-4-yl)-2-methyl-4-oxo-butyric acid ethyl ester

Conditions	Yield
With thionyl chloride 1.) -15 deg C, 30 min, 2.) 40-45 deg C, 2 h;	69%

4-(2',4'-difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid (112344-52-2) → (+/-)-4-(2',4'-difluorobiphenyl-4-yl)-4-hydroxy-2-methylbutanoic lactone

Conditions	Yield
With potassium hydroxide; sodium tetrahydroborate In water 1) 34-40 deg C, 3 h; 2) 20 deg C, 20 h;	58%

(R)-1-phenyl-ethyl-amine (3886-69-9) + 4-(2',4'-difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid (112344-52-2) → (R)-(+)-flobufen (R)-(+)-1-phenylethylammonium salt

Conditions	Yield
In diethyl ether at 20℃;	56%

(S)-1-phenyl-ethylamine (2627-86-3) + 4-(2',4'-difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid (112344-52-2) → (S)-(-)-flobufen (S)-(-)-1-phenylethylammonium salt

Conditions	Yield
In diethyl ether at 20℃;	55%

morpholine (110-91-8) + 4-(2',4'-difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid (112344-52-2) → 4-(2',4'-Difluoro-biphenyl-4-yl)-2-methyl-1-morpholin-4-yl-butane-1,4-dione

Conditions	Yield
With 1-ethyl-piperidine; chloroformic acid ethyl ester 1.) DMF, CH2Cl2, 30 min, 2.) 20 deh C, 2 h; Yield given. Multistep reaction;

(R)-1-phenyl-ethyl-amine (3886-69-9) + 4-(2',4'-difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid (112344-52-2) → 4-(2',4'-difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid R-(+)-1-phenylethylamide

Conditions	Yield
With 1-ethyl-piperidine; chloroformic acid ethyl ester 1.) DMF, CH2Cl2, 30 min, 2.) 20 deh C, 2 h; Yield given. Multistep reaction;

4-(2',4'-difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid (112344-52-2) + ethylamine (75-04-7) → 4-(2',4'-Difluoro-biphenyl-4-yl)-N-ethyl-2-methyl-4-oxo-butyramide

Conditions	Yield
With 1-ethyl-piperidine; chloroformic acid ethyl ester 1.) DMF, CH2Cl2, 30 min, 2.) 20 deh C, 2 h; Yield given. Multistep reaction;

4-(2',4'-difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid (112344-52-2) + N-butylamine (109-73-9) → N-Butyl-4-(2',4'-difluoro-biphenyl-4-yl)-2-methyl-4-oxo-butyramide

Conditions	Yield
With 1-ethyl-piperidine; chloroformic acid ethyl ester 1.) DMF, CH2Cl2, 30 min, 2.) 20 deh C, 2 h; Yield given. Multistep reaction;

4-(2',4'-difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid (112344-52-2) + GlyOEt*HCl (459-73-4) → [4-(2',4'-Difluoro-biphenyl-4-yl)-2-methyl-4-oxo-butyrylamino]-acetic acid ethyl ester

Conditions	Yield
With 1-ethyl-piperidine; chloroformic acid ethyl ester 1.) DMF, CH2Cl2, 30 min, 2.) 20 deh C, 2 h; Yield given. Multistep reaction;

4-(2',4'-difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid (112344-52-2) + benzylamine (100-46-9) → N-Benzyl-4-(2',4'-difluoro-biphenyl-4-yl)-2-methyl-4-oxo-butyramide

Conditions	Yield
With 1-ethyl-piperidine; chloroformic acid ethyl ester 1.) DMF, CH2Cl2, 30 min, 2.) 20 deh C, 2 h; Yield given. Multistep reaction;

Upstream product

• 37847-52-2 2,4-difluorobiphenyl 
• 4100-80-5 2-methylsuccinic anhydride 
• 2170-03-8 itaconic acid anhydride 
• 161692-81-5 4-(2',4'-difluorobiphenyl-4-yl)-2-methylene-4-oxobutanoic acid 
• 97-65-4 2-methylenesuccinic acid 

Related news

Metabolic pathways of flobufen (cas 112344-52-2) — a new antirheumatic and antiarthritic drug. Interspecies comparison07/22/2019

SummaryMetabolic transformations of flobufen, [4-(2′,4′-difluorobiphenyl-4-yl)-4-oxo-2-methylbutanoic acid], a non-steroid antiinflammatory agent, were studied in vitro using the following biological models and species: rat and mouse liver homogenates and liver subcellular fractions (5 000 g a...detailed

Structural study of flobufen (cas 112344-52-2) II. An unexpected role of packing effects on the dihedral angle of phenyl rings in crystal structures of 2,4-difluorobiphenyls07/20/2019

The absolute structure of the (R)-(+)-1-phenylethylammonium salt of (R)-(+)-flobufen (4-(2′,4′-difluorobiphenyl-4-yl)-2-methyl-4oxobutanoic acid) was determined by a single-crystal X-ray study. Comparison of the structure of this flobufen salt with those of flobufen and dehydroflobufen (4-(2′...detailed

Liquid chromatographic–electrospray mass spectrometric determination (LC–ESI-MS) of phase II metabolites of flobufen (cas 112344-52-2) in rat liver microsomes—Chiral discrimination07/19/2019

Glucuronidation of the non-steroidal anti-inflammatory chiral drug flobufen and its major metabolite M17203 has been implicated as an important mechanism of flobufen elimination. To characterize flobufen metabolism by O-glucuronidation, new liquid chromatographic method (LC) coupled with ESI-MS ...detailed

Relevant articles and documents

4-(2',4'-DIFLUOROBIPHENYL-4-YL)-2-METHYL-4-OXOBUTANOIC ACID AND ITS DERIVATIVES

Friedel-Crafts reaction of itaconic anhydride (III) with 2,4-difluorobiphenyl (II) afforded unsaturated acid IV which was hydrogenated to give 4-(2',4'-difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acod (I).A series of functional derivatives and salts of the acid I has been prepared.The antiinflammatory effect of these compounds was compared with that of acid I using selected experimental inflammation models.The analgesic activity in the intraperitoneal iritation test was also evaluated.In the case of (R)-(+)-1-phenylethylamide Vf the ratio of the diastereisomers was determined by HPLC.