89796-99-6

Basic information

• Product Name: Aceclofenac
• Synonyms: ACECLOFENAC;ACECLOFENAC-D2;Airtal;Falcol;Gerbin;Glycolic Acid [o-(2,6-Dichloroanilino)phenyl]acetate Ester;PR-82/3;Preservex
• CAS NO: 89796-99-6
• Molecular Formula: C₁₆H₁₃Cl₂NO₄
• Molecular Weight: 354.18
• EINECS: 205-783-4
• Product Categories: Active Pharmaceutical Ingredients;Intermediates & Fine Chemicals;Pharmaceuticals;Lipid signaling;Aromatics;Free Base API;API;AIRTAL
• Mol File: 89796-99-6.mol
• Article Data: 9

Chemical Properties

• Melting Point: 149-153°C
• Boiling Point: 486 °C at 760 mmHg
• Flash Point: 247.7 °C
• Appearance: off-white to light tan/
• Density: 1.455 g/cm³
• Vapor Pressure: 2.93E-10mmHg at 25°C
• Refractive Index: 1.639
• Storage Temp.: -20°C Freezer
• Solubility: Soluble in DMSO
• PKA: 2.60±0.10(Predicted)
• Water Solubility: 32mg/L(32 oC)
• Merck: 14,22
• CAS DataBase Reference: Aceclofenac(CAS DataBase Reference)
• NIST Chemistry Reference: Aceclofenac(89796-99-6)
• EPA Substance Registry System: Aceclofenac(89796-99-6)

Safety Data

• Hazard Codes: T,N
• Statements: 25-36-50/53
• Safety Statements: 26-45-60-61
• RIDADR: UN 2811 6.1 / PGIII
• WGK Germany: 3
• RTECS: CY1577900
• HazardClass: 6.1
• PackingGroup: III
• Hazardous Substances Data: 89796-99-6(Hazardous Substances Data)

Usage

Description

Different sources of media describe the Description of 89796-99-6 differently. You can refer to the following data:
1. Aceclofenac is a non-steroidal anti-inflammatory drug (NSAIDs) that is commonly prescribed for people with painful rheumatic conditions such as rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. The drug should not be given to children, breastfeeding mothers, and people with porphyria. Pregnant women should not also be given aceclofenac as they risk developing patent ductus arteriosus in the neonate.
2. Aceclofenac is a nonsteroidal antiinflammatory agent with analgesic and antipyretic properties. It is reported to be useful in the treatment of osteoarthritis, rheumatoid arthritis and pain associated with minor surgical procedures. Compared to ketoprofen in the treatment of rheumatoid arthritis, aceclofenac is substantially faster acting.

Mechanism of Action

Aceclofenac acts by inhibiting the effect of natural substances known as cyclooxygenase (COX) enzymes. Notably, these enzymes are responsible for making other chemicals in the body, namely prostaglandins. The prostaglandins are normally produced at sites of damages or injury cause inflammation and pain. By blocking the influence of COX enzymes, production of prostaglandins is minimized, meaning that the swelling and pain is eased.

Precautions

Before taking aceclofenac, it is essential to tell the doctor if one has ever had an allergic reaction to any other NSAID, for instance, diclofenac, aspirin, indomethacin, and naproxen; whether one has allergic disorders such as asthma. It is important to alert the doctor if an individual has a heart condition or problem with circulation or blood vessels. Moreover, inform the physician if one has connective tissue disorder, for instance, lupus erythematosus. One should not take the drug if he/she has high blood pressure or has blood-clotting problems.

Chemical Properties

White Crystalline Solid

Originator

Prodes (Prodesfarma) (Spain)

Uses

Different sources of media describe the Uses of 89796-99-6 differently. You can refer to the following data:
1. Labeled Aceclofenac, intended for use as an internal standard for the quantification of Aceclofenac by GC- or LC-mass spectrometry.
2. Aceclofenac is a non-steroidal, anti-inflammatory drug (NSAID) with potent inhibitory activity in several models of inflammation. It is used for the treatment of osteoarthritis and rheumatoid arthritis. It is a Biopharmaceutics classification system class II (BCS class I) drug which has an intermediate half-life of 3-4h and undergoes substantial first pass metabolism. aceclofenac is available either in oral form (tablet) or in topical form (gel).

Definition

ChEBI: Aceclofenac is a monocarboxylic acid that is the carboxymethyl ester of diclofenac. A non-steroidal anti-inflammatory drug related to diclofenac, it is used in the management of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis. It has a role as an EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor, a non-steroidal anti-inflammatory drug and a non-narcotic analgesic. It is a monocarboxylic acid, a carboxylic ester, a secondary amino compound, an amino acid and a dichlorobenzene. It derives from a diclofenac.

Brand name

Airtal; Gerbin

Biochem/physiol Actions

Non-steroidal, anti-inflammatory drug (NSAID), with selectivity for COX-2 over COX-1.

Drug interactions

Potentially hazardous interactions with other drugs ACE inhibitors and angiotensin-II antagonists: antagonism of hypotensive effect; increased risk of nephrotoxicity and hyperkalaemia. Analgesics: avoid concomitant use of 2 or more NSAIDs, including aspirin (increased side effects); avoid with ketorolac (increased risk of side effects and haemorrhage). Antibacterials: possible increased risk of convulsions with quinolones. Anticoagulants: effects of coumarins and phenindione enhanced; possibly increased risk of bleeding with heparins, dabigatran and edoxaban - avoid long term use with edoxaban. Antidepressants: increased risk of bleeding with SSRIs and venlaflaxine. Antidiabetic agents: effects of sulphonylureas enhanced. Antiepileptics: possibly increased phenytoin concentration. Antivirals: increased risk of haematological toxicity with zidovudine; concentration possibly increased by ritonavir. Ciclosporin: may potentiate nephrotoxicity Cytotoxics: reduced excretion of methotrexate; increased risk of bleeding with erlotinib. Diuretics: increased risk of nephrotoxicity; antagonism of diuretic effect, hyperkalaemia with potassium-sparing diuretics. Lithium: excretion decreased. Pentoxifylline: increased risk of bleeding. Tacrolimus: increased risk of nephrotoxicity.

Metabolism

About two-thirds of a dose is excreted in the urine, mainly as hydroxymetabolites, the principal one being 4-hydroxyaceclofenac. A small amount is converted to diclofenac.

InChI:InChI=1/C16H13Cl2NO4/c17-11-5-3-6-12(18)16(11)19-13-7-2-1-4-10(13)8-15(22)23-9-14(20)21/h1-7,19H,8-9H2,(H,20,21)

Synthetic route

2-((2,6-dichlorophenyl)amino)phenylacetoxyacetic acid tert-butyl ester (139272-68-7) → aceclofenac (89796-99-6)

Conditions	Yield
With hydrogenchloride; acetic anhydride; acetic acid In water at 60℃; for 3h; Temperature;	98.5%
With formic acid In acetone at 65℃; for 0.166667h; Reagent/catalyst; Solvent; Temperature; Microwave irradiation;	96.3%
With aluminum (III) chloride; acetic anhydride; acetic acid at 60 - 65℃; for 2.5h; Reagent/catalyst; Temperature; Large scale;	83%
With trifluoroacetic acid In dichloromethane at 20℃; for 7h;	57%
With formic acid at 40℃;

tert-butyl-[2-(2,6-dichloroanilino) phenyl] acetoxy acetate → aceclofenac (89796-99-6)

Conditions	Yield
With formic acid In toluene at 0 - 35℃; for 2h; Product distribution / selectivity;	95%
With formic acid; trifluoroacetic acid In toluene at 25 - 40℃; for 2.5 - 5.5h; Product distribution / selectivity;
With formic acid In toluene at 0 - 50℃; for 2 - 4.5h; Product distribution / selectivity;

aceclofenac benzyl ester (100499-89-6) → aceclofenac (89796-99-6)

Conditions	Yield
With hydrogen; palladium on activated charcoal

diclofenac sodium (15307-79-6) → aceclofenac (89796-99-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: dimethylformamide 2: H2 / Pd/C View Scheme
Multi-step reaction with 2 steps 1: potassium iodide / acetonitrile / 0.25 h / 30 °C / Microwave irradiation 2: formic acid / acetone / 0.17 h / 65 °C / Microwave irradiation View Scheme
Multi-step reaction with 2 steps 1: potassium iodide / ethanol / 3 h / 61 - 65 °C / Large scale 2: acetic acid; acetic anhydride; aluminum (III) chloride / 2.5 h / 60 - 65 °C / Large scale View Scheme

C35H29Cl2NO10 → aceclofenac (89796-99-6)

Conditions	Yield
With simulated intestinalfluid In methanol at 37℃; pH=7.4; Reagent/catalyst; pH-value; Solvent;

1,10-Phenanthroline (66-71-7) + zirconyl nitrate + water (7732-18-5) + aceclofenac (89796-99-6) → C28H22Cl2N3O6Zr(1+)*NO3(1-)*9H2O

Conditions	Yield
With potassium hydroxide In acetone for 8h; Reflux;	89.35%

aceclofenac (89796-99-6) → C16H13Cl2NO5 + C14H11Cl2NO3 + 2-[(2,6-dichlorophenyl)amino]phenylacetic acid methyl ester (15307-78-5)

Conditions	Yield
In methanol at 20℃; for 6h; UV-irradiation;	A 7% B 5% C 88%

1,10-Phenanthroline (66-71-7) + copper(II) acetate monohydrate (6046-93-1) + aceclofenac (89796-99-6) → C28H24Cl2CuN3O6(1+)*C2H3O2(1-)*6H2O

Conditions	Yield
With potassium hydroxide In acetone for 8h; Reflux;	80.04%

1,10-Phenanthroline (66-71-7) + nickel(II) acetate tetrahydrate (6018-89-9) + aceclofenac (89796-99-6) → C28H24Cl2N3NiO6(1+)*C2H3O2(1-)*3H2O

Conditions	Yield
With potassium hydroxide In acetone for 8h; Reflux;	78.08%

1,10-Phenanthroline (66-71-7) + lanthanide(III)chloride heptahydrate + aceclofenac (89796-99-6) → C28H24Cl2LaN3O6(2+)*9H2O*2Cl(1-)

Conditions	Yield
With potassium hydroxide In acetone for 8h; Reflux;	76.11%

4-acetaminophenol (103-90-2) + aceclofenac (89796-99-6) → C24H20Cl2N2O5 (1452834-52-4)

Conditions	Yield
With trichlorophosphate In pyridine at 5℃; for 4h;	73%

1,10-Phenanthroline (66-71-7) + zinc(II) acetate dihydrate (5970-45-6) + aceclofenac (89796-99-6) → C28H24Cl2N3O6Zn(1+)*C2H3O2(1-)*3H2O

Conditions	Yield
With potassium hydroxide In acetone for 8h; Reflux;	72.53%

ethanol (64-17-5) + aceclofenac (89796-99-6) → 2-(2-[(2',6'-dichlorophenyl)amino]phenyl)acetoxyacetate

Conditions	Yield
With sulfuric acid for 6h; Reflux;	65%

methanol (67-56-1) + aceclofenac (89796-99-6) → C17H15Cl2NO4 (139272-66-5)

Conditions	Yield
With tert.-butylnitrite at 40℃; for 48h;	63%
With sulfuric acid Reflux;

aceclofenac (89796-99-6) + 1,2:3,4-di-O-isopropylidene-α-D-galactopyranose (4064-06-6) → 1,2,3,4-di-O-isopropylidene-D-α-galactopyranose-6-yl 2-(2-(2-((2,6-dichlorophenyl)amino)phenyl)acetoxy)acetic acid

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 4h;	62%

{(1R,2R)-cyclohexane-1,2-diamine}dichloridoplatinum(II) (38780-40-4, 52691-24-4, 61848-70-2, 61848-66-6, 61848-62-2) + aceclofenac (89796-99-6) → C22H26Cl3N3O4Pt

Conditions	Yield
With sodium carbonate; silver nitrate In N,N-dimethyl-formamide at 20℃; for 24h; Darkness;	50%

potassium ethyl methylmalonate (103362-70-5) + aceclofenac (89796-99-6) → ethyl 4-(2-(2-((2,6-dichlorophenyl)amino)phenyl)acetoxy)-2-methyl-3-oxobutanoate

Conditions	Yield
Stage #1: aceclofenac With 1,1'-carbonyldiimidazole Inert atmosphere; Stage #2: potassium ethyl methylmalonate With magnesium chloride Inert atmosphere;	43%

trans-2-pentenal (1576-87-0) + tert-butylisonitrile (119072-55-8, 7188-38-7) + tert-butyl N-tosyloxycarbamate (105838-14-0) + aceclofenac (89796-99-6) → tert-butyl (2S,3R)-2-{2-(tert-butylamino)-1-[2-(2-{2-[(2,6-dichlorophenyl)amino]phenyl}acetoxy)acetoxy]-2-oxoethyl}-3-ethylaziridine-1-carboxylate

Conditions	Yield
Stage #1: trans-2-pentenal; tert-butyl N-tosyloxycarbamate With (S)-α,α-bis(4-hexylphenylthio)-2-pyrrolidinemethanol trimethylsilylether; sodium carbonate In ethanol; water at 20℃; for 0.666667h; Green chemistry; Stage #2: tert-butylisonitrile; aceclofenac In ethanol; water at 20℃; for 24h; Passerini Condensation; Green chemistry; diastereoselective reaction;	33%

2-nitroxyethylammonium nitrate (4665-58-1) + aceclofenac (89796-99-6) → (N-(2-(nitrooxy)ethyl)carbamoyl)methyl 2-(2-((2,6-dichlorophenyl)-amino)phenyl)acetate (183195-09-7)

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride	13%

aceclofenac (89796-99-6) → [2-(2,6-dichloroanilino)phenyl]acetic acid (15307-86-5)

Conditions	Yield
With sodium hydroxide for 3h; Heating;

aceclofenac (89796-99-6) → 4'-hydroxy aceclofenac

Conditions	Yield
With NADPH-generating system In acetonitrile at 37℃; for 3h; pH=7.4; aq. phosphate buffer;

aceclofenac (89796-99-6) + β-cyclodextrine → aceclofenac-β-cyclodextrin (1:1) inclusion complex

Conditions	Yield
In methanol; water for 0.75h;

formaldehyd (50-00-0) + 3,6-dinitro-9H-carbazole (3244-54-0) + aceclofenac (89796-99-6) → C29H20Cl2N4O8 (1246212-64-5)

Conditions	Yield
In methanol Mannich reaction; Cooling with ice; Reflux;

3,6-dinitro-9H-carbazole (3244-54-0) + benzaldehyde (100-52-7) + aceclofenac (89796-99-6) → C35H24Cl2N4O8 (1246212-56-5)

Conditions	Yield
In methanol Mannich reaction; Cooling with ice; Reflux;

3,6-dinitro-9H-carbazole (3244-54-0) + aceclofenac (89796-99-6) + acetaldehyde (75-07-0) → C30H22Cl2N4O8 (1246212-52-1)

Conditions	Yield
In methanol Mannich reaction; Cooling with ice; Reflux;

3,6-dinitro-9H-carbazole (3244-54-0) + aceclofenac (89796-99-6) + 4-dimethylamino-benzaldehyde (100-10-7) → C37H29Cl2N5O8 (1246212-60-1)

Conditions	Yield
In methanol Mannich reaction; Cooling with ice; Reflux;

aceclofenac (89796-99-6) → 2-chloro-2-oxoethyl 2-(2-((2,6-dichlorophenyl)amino)phenyl)acetate (1227857-41-1)

Conditions	Yield
With thionyl chloride In benzene
With thionyl chloride at 20℃; for 18h; Temperature;
With thionyl chloride In tetrahydrofuran for 1.5h; Microwave irradiation;

aceclofenac (89796-99-6) → 2-[(2,6-dichlorophenyl)amino]-N1-(phenyl)-N4-phenylacetoxyacetamidobenzenesulfonamide (1262333-96-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: thionyl chloride / benzene 2: N,N-dimethyl-formamide / 24 h / 10 - 130 °C View Scheme

Upstream product

• 139272-68-7 2-((2,6-dichlorophenyl)amino)phenylacetoxyacetic acid tert-butyl ester 
• 15307-79-6 diclofenac sodium 
• 100499-89-6 aceclofenac benzyl ester 

Downstream Products

• 15307-86-5 [2-(2,6-dichloroanilino)phenyl]acetic acid 
• 15307-78-5 2-[(2,6-dichlorophenyl)amino]phenylacetic acid methyl ester 
• 229308-90-1 4'-hydroxy aceclofenac 
• 139272-67-6 2-(2-[(2',6'-dichlorophenyl)amino]phenyl)acetoxyacetate 

Relevant articles and documents

Method for industrially producing aceclofenac

The invention relates to a method for industrially producing aceclofenac. The method comprises the following steps: mixing organic acid, a water removal agent and Lewis acid, fully stirring, and adding aceclofenac tert-butyl ester for acidolysis reaction. The method is mild in reaction condition, high in reaction rate, free of high temperature and high energy consumption, easy and convenient to operate, environmentally friendly, economical and free of participation or generation of major pollutants, most solvents can be recycled, emission of waste solvents is reduced, and therefore the cost isreduced, and the environment is protected.

Preparation method of aceclofenac

The invention discloses a microwave-assisted preparation method of aceclofenac. The method is as follows: under the microwave condition, a compound 2 and a compound 3 are reacted to form a compound 4under the catalysis of KI; and under the microwave condition, a reaction of the compound 4 is carried out in a mixed solvent of formic acid and acetone. According to the method, the acidolysis of aceclofenac tert-butyl ester is carried out in the mixture of formic acid and acetone under the microwave condition, the acidolysis method has high selectivity, the fracture of the ethoxyl group in aceclofenac tert-butyl ester is reduced to the lowest limit, the conversion rate of the acidolysis reaction is high, the diclofenac content in the product is extremely small, the product is easy to refine,and the purity is high.

Synthesis and pharmacological evaluation of mutual prodrugs of aceclofenac with quercetin, vanillin and l-tryptophan as gastrosparing NSAIDS

Synthesis, physicochemical characterization and pharmacological evaluation of mutual prodrugs of aceclofenac with quercetin, vanillin and l-tryptophan have been attempted to develop novel gastrosparing NSAIDs, devoid of ulcerogenic side effects. The structures of synthesized prodrugs were confirmed by IR, 1H NMR, 13C NMR and mass spectroscopy. The hydrolysis kinetics studies were performed in simulated gastric fluid, simulated intestinal fluid and rat fecal matter. Its anti-inflammatory and ulcer index were analyzed along with estimation of biochemical parameters (GWM and Hexosamine), oxidative parameters (LPO, GSH, CAT, and SOD) and protein estimation. The results indicated that the synthesized prodrugs are chemically stable, biolabile and possesses optimum lipophilicity. They also exhibited retention of anti-inflammatory activity with reduced ulcerogenicity. The study showed that the mutual prodrugs are better in action compared to the parent drug and have fewer gastrointestinal side effects.