15307-79-6

Basic information

• Product Name: Diclofenac sodium
• Synonyms: N-(2,6-Dichlorophenyl)-o-aminophenylacetic acid sodium salt;OOTHECA MANTIDIS;Diclofenac SodiuM EC pellets 32%;Diclofenac SodiuM SR pellets 32%;Diclofenac Sodium (200 mg);DelphiMix;Diacron;Naclof
• CAS NO: 15307-79-6
• Molecular Formula: C₁₄H₁₀Cl₂NO₂*Na
• Molecular Weight: 318.13
• EINECS: 239-346-4
• Product Categories: Lipid signaling;Amines;Aromatics;Heterocycles;VOLATREN;Other APIs;Active Pharmaceutical Ingredients;Organics;Intermediates & Fine Chemicals;Pharmaceuticals;Steroids;API's
• Mol File: 15307-79-6.mol

Chemical Properties

• Melting Point: 288-290°C
• Boiling Point: 412 °C at 760 mmHg
• Flash Point: 203 °C
• Appearance: white or off-white powder
• Density: 0.781 g/cm3
• Storage Temp.: -20°C Freezer
• Solubility: H2O: 50 mg/mL
• PKA: 4(at 25℃)
• Water Solubility: Soluble in water to 50mg/ml.
• Stability: Stable.
• Merck: 14,3081
• CAS DataBase Reference: Diclofenac sodium(CAS DataBase Reference)
• NIST Chemistry Reference: Diclofenac sodium(15307-79-6)
• EPA Substance Registry System: Diclofenac sodium(15307-79-6)

Safety Data

• Hazard Codes: T,Xi
• Statements: 25-36/37/38-63
• Safety Statements: 22-36/37-45-36-26-60-20
• RIDADR: UN 2811 6.1/PG 3
• WGK Germany: 3
• RTECS: AG6330000
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 15307-79-6(Hazardous Substances Data)

Usage

Chemical Description

Diclofenac sodium is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain and inflammation.

Uses

1. Used in Pharmaceutical Industry:
Diclofenac sodium is used as a pharmaceutical secondary standard for quality control, providing a convenient and cost-effective alternative to the preparation of in-house working standards.
2. Used in Pain Management:
Diclofenac sodium is used as an analgesic for the treatment of acute pain and inflammation, effective in various acute forms of pain.
3. Used in Inflammation Treatment:
Diclofenac sodium is used as an anti-inflammatory agent, treating conditions such as osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis.
4. Used in Antipyretic Applications:
Diclofenac sodium is used to reduce fever by inhibiting the formation of prostaglandins involved in fever regulation.
5. Used in Transdermal Drug Delivery:
Diclofenac sodium is used in transdermal administration, inhibiting carrageenan-induced paw edema in rats, and providing a non-invasive method for pain relief.
6. Used in Stabilizing Transthyretin:
Diclofenac sodium is used to stabilize the native tetrameric conformation of transthyretin (TTR) fibrils, preventing the formation of insoluble amyloidogenic TTR deposits.
7. Used in Inhibiting Cyclooxygenase (COX):
Diclofenac sodium is used as an inhibitor of COX-1 and COX-2, suppressing prostaglandin E2 synthesis and producing anti-inflammatory and analgesic effects.
8. Used in Parenteral Formulation:
Due to its poor solubility, diclofenac sodium is used in parenteral formulations containing solvents like propylene glycol and benzyl alcohol, allowing for intramuscular and intravenous administration.

Mechanisms of action

Putative mechanisms of action of diclofenac may include inhibition of leukotriene synthesis, inhibition of phospholipase A2, modulation of free arachidonic acid levels, stimulation of adenosine triphosphate-sensitive potassium channels via the L-arginine-nitric oxide-cyclic guanosine monophosphate pathway and centrally mediated and neuropathic mechanisms. Other emerging mechanisms of action may include inhibition of peroxisome proliferator activated receptor-c, reduction in plasma and synovial substance P and interleukin-6 levels, inhibition of the thromboxane-prostanoid receptor and inhibition of acid-sensing ion channels.

Clinical Application

Clinical trials have demonstrated the analgesic efficacy of diclofenac sodium in terms of relieving moderate to severe postoperative pain in patients undergoing dental surgery or minor orthopaedic surgery. Subcutaneous diclofenac sodium also effectively relieved moderate to severe neuropathic pain, related to cancer or not. Diclofenac sodium was generally well tolerated in clinical trials, with injection-site reactions among the most commonly reported adverse events.

Originator

Voltaren,Fujisawa,Japan,1974

Manufacturing Process

Four grams of N-chloroacetyl-N-phenyl-2,6-dichloroaniline and 4 grams of aluminum chloride are well mixed together and heated for 2 hours at 160°C. The melt is cooled and poured onto about 50 grams of ice while it is still warm. The oil which separates is dissolved in 50 ml of chloroform, the chloroform solution is washed with 10 ml of water, dried over sodium sulfate and concentrated under 11 torr. The residue is distilled. The 1-(2,6- dichlorophenyl)-2-indolinone melts at 126°-127°C.A solution of 186 grams of 1-(2,6-dichlorophenyl)-2-indolinone in 660 ml of ethanol and 660 ml of 2 N sodium hydroxide solution is refluxed for 4 hours. The solution is then cooled and left to stand for 4 hours at 0°-5°C. The crystals which form are filtered off and recrystallized from water. The sodium salt of 2-(2,6-dichloroanilino)-phenylacetic acid melts at 283°-285°C. The yield is 97% of theoretical, according to US Patent 3,558,690.

Therapeutic Function

Antiinflammatory

World Health Organization (WHO)

The World Health Organization currently has no information to suggest that diclofenac is less safe than other widely available non-steroidal antiinflammatory substances of this type, or that children are particularly liable to react adversely. It is registered in many countries in several dosage forms, including a 12.5 mg suppository indicated for juvenile arthritis.

Biochem/physiol Actions

Standard NSAID and cyclooxygenase (COX) inhibitor. Major metabolites are 4′-hydroxydiclofenac and 5′-hydroxydiclofenac. Has been used as substrate selective for CYP2C9.

Clinical Use

Diclofenac sodium is indicated for the treatment of rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis.

Veterinary Drugs and Treatments

The equine topical cream (Surpass?) is labeled for the control of pain and inflammation associated with osteoarthritis in tarsal, carpal, metacarpophalangeal, metarsophalangeal, and proximal interphalangeal (hock, knee, fetlock, pastern) joints for use up to 10 days duration. While, theoretically, diclofenac could be used systemically (orally) in other veterinary species, there are approved and safer alternatives.

Drug interactions

Potentially hazardous interactions with other drugs 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: possibly increased risk of convulsions with quinolones; concentration reduced by rifampicin.Anticoagulants: effects of coumarins and phenindione enhanced; possibly increased risk of bleeding with heparins, dabigatran and edoxaban - avoid long term use with edoxaban; increased risk of haemorrhage with IV diclofenac - avoid.Antidepressants: increased risk of bleeding with SSRIs and venlaflaxine.Antidiabetic agents: effects of sulphonylureas enhanced.Antiepileptics: possibly increased phenytoin concentration.Ciclosporin: may potentiate nephrotoxicity; concentration increased by ciclosporin.Cytotoxics: reduced excretion of methotrexate; increased risk of bleeding with erlotinib.

Metabolism

Diclofenac undergoes first-pass metabolism and is It is then excreted in the form of glucuronide and sulfate conjugates, mainly in the urine (about 60%) but also in the bile (about 35%). then extensively metabolised to 4′-hydroxydiclofenac, 5-hydroxydiclofenac, 3′-hydroxydiclofenac, and 4′,5-dihydroxydiclofenac by glucuronidation of the intact molecule or more commonly by single and multiple hydroxylation followed by glucuronidation.

InChI:InChI=1/C12H9Cl2N.C2H4O2.Na/c13-10-7-4-8-11(14)12(10)15-9-5-2-1-3-6-9;1-2(3)4;/h1-8,15H;1H3,(H,3,4);/q;;+1/p-1

Synthetic route

2-[(2,6-dichlorophenyl)amino]phenylacetic acid methyl ester (15307-78-5) → diclofenac sodium (15307-79-6)

Conditions	Yield
With sodium hydroxide In water; N,N-dimethyl-formamide at 80℃; for 24h;	96.1%

1-(2,6-dichlorophenyl)indolin-2-one (15362-40-0) → diclofenac sodium (15307-79-6)

Conditions	Yield
With sodium hydroxide In ethanol; water for 4h; Heating;	93%
With sodium dithionite; water; sodium hydroxide for 6h; Reflux;	92.3%
With sodium hydroxide In ethanol for 3h; Heating;	85%
With N-benzyl-N,N,N-triethylammonium chloride; sodium hydroxide In toluene for 10h; Reflux;	83.6%
With sodium hydroxide for 2h; Temperature; Reflux;	4.035 g

C22H17Cl2NO3 → diclofenac sodium (15307-79-6)

Conditions	Yield
With water; sodium hydroxide In methanol for 6h; Solvent; Reflux;	86%

potassium 2-iodophenylacetate (100754-92-5) + 2,6-Dichloroaniline (608-31-1) → diclofenac sodium (15307-79-6)

Conditions	Yield
With 1-methyl-pyrrolidin-2-one; copper; potassium carbonate at 120℃; for 22h;	56%

2'-chloro-benzeneacetic acid (2444-36-2) + 2,6-Dichloroaniline (608-31-1) + butan-1-ol (71-36-3) → diclofenac sodium (15307-79-6)

Conditions	Yield
With sodium hydroxide; potassium iodide; copper(I) iodide; potassium carbonate In N,N-dimethyl-formamide	42.9%

2'-chloro-benzeneacetic acid (2444-36-2) + 2,6-Dichloroaniline (608-31-1) → diclofenac sodium (15307-79-6)

Conditions	Yield
Stage #1: 2'-chloro-benzeneacetic acid; 2,6-Dichloroaniline With copper(l) iodide; iodine; potassium carbonate; potassium iodide In N,N-dimethyl-formamide for 12h; Inert atmosphere; Schlenk technique; Reflux; Stage #2: With sodium hydroxide In water for 4h; Reflux;	31%

2-(2-((2,6-dichlorophenyl)amino)phenyl)-2-oxoacetic acid (66156-75-0) → diclofenac sodium (15307-79-6)

Conditions	Yield
With sodium methylate; hydrazine hydrate In 2-methoxy-ethanol 1.) from 60 deg C to 150 deg C, 2.) 150 deg C, 1 h; Yield given;

N-phenyl-2,6-dichloroaniline (15307-93-4) → diclofenac sodium (15307-79-6)

Conditions	Yield
Multi-step reaction with 5 steps 1: benzene / 6 h / Heating 2: 91 percent / m-chloroperbenzoic acid / CH2Cl2 / 1 h / Ambient temperature 3: 84 percent / p-toluenesulfonic acid / benzene / 0.5 h / Heating 4: 97 percent / Zn / acetic acid / 4 h / Heating 5: 85 percent / 20percent NaOH / ethanol / 3 h / Heating View Scheme
Multi-step reaction with 5 steps 1: benzene / 6 h / Heating 2: N-chlorosuccinimide / CCl4 / 1 h / Ambient temperature 3: SnCl4 / CCl4 / 0.83 h / Ambient temperature 4: 97 percent / Zn / acetic acid / 4 h / Heating 5: 85 percent / 20percent NaOH / ethanol / 3 h / Heating View Scheme
Multi-step reaction with 4 steps 1: benzene / 2 h / Ambient temperature 2: AlCl3 / various solvent(s) / 20 h / Ambient temperature 3: 1 N NaOH / ethanol; H2O / 0.17 h / Heating 4: hydrazine hydrate, NaOCH3 / 2-methoxy-ethanol / 1.) from 60 deg C to 150 deg C, 2.) 150 deg C, 1 h View Scheme
Multi-step reaction with 3 steps 1: 66 percent / 16 h / Heating 2: 75.4 percent / AlCl3 / 2 h / 160 °C 3: 93 percent / 2 N NaOH / ethanol; H2O / 4 h / Heating View Scheme
Multi-step reaction with 3 steps 1: toluene / 3 h / 120 °C 2: triethylamine hydrochloride-aluminum trichloride / 4.5 h / 20 - 60 °C 3: sodium hydroxide / 2 h / Reflux View Scheme

N-(2,6-dichlorophenyl)-α-(methylthio)acetanilide (83281-93-0) → diclofenac sodium (15307-79-6)

Conditions	Yield
Multi-step reaction with 4 steps 1: 91 percent / m-chloroperbenzoic acid / CH2Cl2 / 1 h / Ambient temperature 2: 84 percent / p-toluenesulfonic acid / benzene / 0.5 h / Heating 3: 97 percent / Zn / acetic acid / 4 h / Heating 4: 85 percent / 20percent NaOH / ethanol / 3 h / Heating View Scheme
Multi-step reaction with 4 steps 1: N-chlorosuccinimide / CCl4 / 1 h / Ambient temperature 2: SnCl4 / CCl4 / 0.83 h / Ambient temperature 3: 97 percent / Zn / acetic acid / 4 h / Heating 4: 85 percent / 20percent NaOH / ethanol / 3 h / Heating View Scheme

1-(2,6-dichlorophenyl)-3-(methylthio)oxindole (83281-94-1) → diclofenac sodium (15307-79-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 97 percent / Zn / acetic acid / 4 h / Heating 2: 85 percent / 20percent NaOH / ethanol / 3 h / Heating View Scheme

N-(2,6-dichlorophenyl)-α-(methylsulfinyl)acetanilide (83281-96-3) → diclofenac sodium (15307-79-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: 84 percent / p-toluenesulfonic acid / benzene / 0.5 h / Heating 2: 97 percent / Zn / acetic acid / 4 h / Heating 3: 85 percent / 20percent NaOH / ethanol / 3 h / Heating View Scheme

α-chloro-N-(2,6-dichlorophenyl)-α-(methylthio)acetanilide → diclofenac sodium (15307-79-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: SnCl4 / CCl4 / 0.83 h / Ambient temperature 2: 97 percent / Zn / acetic acid / 4 h / Heating 3: 85 percent / 20percent NaOH / ethanol / 3 h / Heating View Scheme

1-(2,6-Dichlorphenyl)-2,3-indoldion (24542-74-3) → diclofenac sodium (15307-79-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1 N NaOH / ethanol; H2O / 0.17 h / Heating 2: hydrazine hydrate, NaOCH3 / 2-methoxy-ethanol / 1.) from 60 deg C to 150 deg C, 2.) 150 deg C, 1 h View Scheme

[(2,6-Dichloro-phenyl)-phenyl-amino]-oxo-acetyl chloride (24542-55-0) → diclofenac sodium (15307-79-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: AlCl3 / various solvent(s) / 20 h / Ambient temperature 2: 1 N NaOH / ethanol; H2O / 0.17 h / Heating 3: hydrazine hydrate, NaOCH3 / 2-methoxy-ethanol / 1.) from 60 deg C to 150 deg C, 2.) 150 deg C, 1 h View Scheme

2-chloro-N-(2',6'-dichlorophenyl)-N-phenylacetamide (15308-01-7) → diclofenac sodium (15307-79-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 75.4 percent / AlCl3 / 2 h / 160 °C 2: 93 percent / 2 N NaOH / ethanol; H2O / 4 h / Heating View Scheme

N-(2,6-dichlorophenyl)phenylacetamide → diclofenac sodium (15307-79-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: tert-butylhypochlorite / dichloromethane / 10 h / 25 °C / Cooling with ice 2: aluminum (III) chloride / dichloromethane / 12 h / 20 °C / Cooling with ice 3: N-benzyl-N,N,N-triethylammonium chloride; sodium hydroxide / toluene / 10 h / Reflux View Scheme

2,6-Dichloroaniline (608-31-1) → diclofenac sodium (15307-79-6)

Conditions	Yield
Multi-step reaction with 4 steps 1: calcium chloride; pyridine / 4 h / Reflux; Cooling with ice 2: tert-butylhypochlorite / dichloromethane / 10 h / 25 °C / Cooling with ice 3: aluminum (III) chloride / dichloromethane / 12 h / 20 °C / Cooling with ice 4: N-benzyl-N,N,N-triethylammonium chloride; sodium hydroxide / toluene / 10 h / Reflux View Scheme

phenylacetyl chloride (103-80-0) → diclofenac sodium (15307-79-6)

Conditions	Yield
Multi-step reaction with 4 steps 1: calcium chloride; pyridine / 4 h / Reflux; Cooling with ice 2: tert-butylhypochlorite / dichloromethane / 10 h / 25 °C / Cooling with ice 3: aluminum (III) chloride / dichloromethane / 12 h / 20 °C / Cooling with ice 4: N-benzyl-N,N,N-triethylammonium chloride; sodium hydroxide / toluene / 10 h / Reflux View Scheme

(2-benzoylamino-phenyl)-acetic acid methyl ester (3559-26-0) → diclofenac sodium (15307-79-6)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: thionyl chloride / 3 h / Reflux 1.2: 3 h / Cooling with ice; Reflux 2.1: diphenylether / 3 h / Reflux 3.1: sodium hydroxide; water / methanol / 6 h / Reflux View Scheme

methyl (2-nitrophenyl)acetate (30095-98-8) → diclofenac sodium (15307-79-6)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: palladium on activated charcoal; hydrogen / toluene / 5 °C / 760.05 Torr 2.1: triethylamine / toluene / 2 h / 0 °C 3.1: thionyl chloride / 3 h / Reflux 3.2: 3 h / Cooling with ice; Reflux 4.1: diphenylether / 3 h / Reflux 5.1: sodium hydroxide; water / methanol / 6 h / Reflux View Scheme

benzeneacetic acid methyl ester (101-41-7) → diclofenac sodium (15307-79-6)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: nitric acid / dichloromethane / 24 h / 0 - 20 °C 2.1: palladium on activated charcoal; hydrogen / toluene / 5 °C / 760.05 Torr 3.1: triethylamine / toluene / 2 h / 0 °C 4.1: thionyl chloride / 3 h / Reflux 4.2: 3 h / Cooling with ice; Reflux 5.1: diphenylether / 3 h / Reflux 6.1: sodium hydroxide; water / methanol / 6 h / Reflux View Scheme

2-aminophenylacetic acid methyl ester (35613-44-6) → diclofenac sodium (15307-79-6)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: triethylamine / toluene / 2 h / 0 °C 2.1: thionyl chloride / 3 h / Reflux 2.2: 3 h / Cooling with ice; Reflux 3.1: diphenylether / 3 h / Reflux 4.1: sodium hydroxide; water / methanol / 6 h / Reflux View Scheme

didecyldimethylammonium chloride (7173-51-5) + diclofenac sodium (15307-79-6) → diclofenac didecyldimethylammonium salt (934544-42-0)

Conditions	Yield
In water at 20℃; for 0.5h; Product distribution / selectivity;	100%

diclofenac sodium (15307-79-6) + cadmium(II) chloride (10108-64-2) → {Cd(C6H3Cl2NHC6H4CH2COO)2(H2O)} (149753-43-5)

Conditions	Yield
With H2O; KOH In water byproducts: NaCl; mixing aq. soln. of the components, adjusting to pH 5.5-7.5 with KOH and stirring at room temp. for 4-6 h; filtn., washing with water, drying over silica gel (vac.) and over P4O10 at 90°C (vac.);	100%

diclofenac sodium (15307-79-6) + zinc(II) chloride (7646-85-7) → {Zn(C6H3Cl2NHC6H4CH2COO)2(H2O)} (149753-42-4)

Conditions	Yield
With H2O; KOH In water byproducts: NaCl; mixing aq. soln. of the components, adjusting to pH 5.5-7.5 with KOH and stirring at room temp. for 4-6 h; filtn., washing with water, drying over silica gel (vac.) and over P4O10 at 90°C (vac.);	100%

diclofenac sodium (15307-79-6) → [2-(2,6-dichloroanilino)phenyl]acetic acid (15307-86-5)

Conditions	Yield
With hydrogenchloride In water; acetone at 20 - 45℃; for 3h; pH=1.4 - 1.6; Solvent;	99%
With hydrogenchloride In water Cooling with ice;	90%
With hydrogenchloride In water at 0 - 20℃;	70%

diclofenac sodium (15307-79-6) → 1-(2,6-dichlorophenyl)-1,3-dihydro-indol-2-one-[3,3,5,7-D4] (1401311-49-6)

Conditions	Yield
With water-d2; hydrogen chloride at 160℃; for 0.333333h; Microwave irradiation;	96%

choline chloride (67-48-1) + diclofenac sodium (15307-79-6) → (2-hydroxyethyl)tri-methylammonium [o-(2,6-dichloroanilino)phenyl]acetate (148439-51-4)

Conditions	Yield
In ethanol at 20℃; for 1h;	96%

diclofenac sodium (15307-79-6) + 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide (572-09-8) → 1-O-<2-<(2,6-dichlorophenyl)amino>phenylacetyl>-2,3,4,6-tetra-O-acetyl-β-D-glucopyranose (87906-12-5)

Conditions	Yield
citrimide In water; 1,2-dichloro-ethane Ambient temperature;	95%

bromoacetic acid tert-butyl ester (5292-43-3) + diclofenac sodium (15307-79-6) → 2-((2,6-dichlorophenyl)amino)phenylacetoxyacetic acid tert-butyl ester (139272-68-7)

Conditions	Yield
With potassium iodide In ethanol at 61 - 65℃; for 3h; Temperature; Large scale;	94.45%
With potassium iodide In acetonitrile at 30℃; for 0.25h; Microwave irradiation;	91.6%
With tetra(n-butyl)ammonium hydrogensulfate; potassium iodide In water; acetone at 60 - 65℃; for 2h;	17.3 g
In N,N-dimethyl-formamide at 20 - 45℃;

4-methyloxetan-2-one (3068-88-0, 32082-74-9, 36536-46-6, 65058-82-4) + diclofenac sodium (15307-79-6) → Reaxys ID: 15741354

Conditions	Yield
In dimethyl sulfoxide at 20℃;	94%

diclofenac sodium (15307-79-6) → C14H3(2)H6Cl2NO

Conditions	Yield
With trifluoroacetic acid-d1 at 110℃; for 16h; Sealed tube;	94%

4,4'-bipyridine (553-26-4) + diclofenac sodium (15307-79-6) + silver nitrate → Ag(2-(2,6-dicholoroanilino)phenylacetic acid)(4,4'-bipyridine)

Conditions	Yield
In water; acetonitrile at 50℃;	94%

diclofenac sodium (15307-79-6) + 3-(bromomethyl)-4-methyl-1,2,5-oxadiazole-2-oxide (169614-77-1) → [2-(2,6-dichlorophenylamino)-phenyl]-acetic acid 4-methyl-2-oxy-furazan-3-ylmethyl ester

Conditions	Yield
In N,N-dimethyl-formamide at 20 - 25℃; for 2h;	93%

2-(2-Hydroxyethyl)pyridine (103-74-2) + diclofenac sodium (15307-79-6) + copper(II) acetate monohydrate (6046-93-1) → C42H36Cl4Cu2N4O6

Conditions	Yield
In methanol at 50℃;	91%

diclofenac sodium (15307-79-6) + N,N-didecyl-N,N-dimethylammonium bromide (2390-68-3) → diclofenac didecyldimethylammonium salt (934544-42-0)

Conditions	Yield
With sodium hydrogencarbonate; sodium hydroxide In methanol; water at 20℃; for 0.5h;	91%

diclofenac sodium (15307-79-6) + methyl iodide (74-88-4) → 2-[(2,6-dichlorophenyl)amino]phenylacetic acid methyl ester (15307-78-5)

Conditions	Yield
In N,N-dimethyl-formamide	90%
In acetone Heating;

copper(ll) sulfate pentahydrate + diclofenac sodium (15307-79-6) → 2C14H10Cl2NO2(1-)*Cu(2+)*2H2O

Conditions	Yield
In water at 20℃;	90%

tert-Butyl chloroacetate (107-59-5) + diclofenac sodium (15307-79-6) → 2-((2,6-dichlorophenyl)amino)phenylacetoxyacetic acid tert-butyl ester (139272-68-7)

Conditions	Yield
With sodium iodide In acetonitrile at 77 - 78℃; for 2h;	89.6%
In acetonitrile for 4h; Reflux;
With potassium iodide In N,N-dimethyl-formamide for 2h; Reflux; Large scale;	25.5 g

diclofenac sodium (15307-79-6) + 6-bromomethyl-benzo[1,2,5]oxadiazole-1-oxide → [2-(2,6-dichlorophenylamino)-phenyl]-acetic acid 1-oxy-benzo[1,2,5]oxadiazol-6-ylmethyl ester

Conditions	Yield
In N,N-dimethyl-formamide at 20 - 25℃; for 2h;	89%

diclofenac sodium (15307-79-6) + 5-(bromomethyl)benzofuroxan (175609-21-9) → given name is incorrect (883738-54-3)

Conditions	Yield
With N-Bromosuccinimide; dibenzoyl peroxide In N,N-dimethyl-formamide at 25℃; for 2h;	89%

2-(2-Hydroxyethyl)pyridine (103-74-2) + nickel(II) chloride hexahydrate + diclofenac sodium (15307-79-6) → [Ni(diclofenac)2(2-pyridineethanol)2]

Conditions	Yield
In methanol at 50℃;	89%

methanol (67-56-1) + diclofenac sodium (15307-79-6) + copper(II) nitrate → tetrakis{μ-2-[2-(2,6-dichloroanilino)phenyl]acetato-κ2O:O'}bis(methanol-κO)copper(II)

Conditions	Yield
In water at 20℃;	89%

1H-imidazole (288-32-4) + diclofenac sodium (15307-79-6) + copper(II) nitrate → bis{2-[2-(2,6-dichloroanilino)phenyl]acetato-κ2O,O'}bis(1H-imidazole-κN3)copper(II)

Conditions	Yield
In methanol; water at 20℃;	89%

didecyldimethylammonium acesulfamate (934544-25-9) + diclofenac sodium (15307-79-6) → diclofenac didecyldimethylammonium salt (934544-42-0)

Conditions	Yield
In acetone at 60℃; for 2h; Product distribution / selectivity;	88%

diclofenac sodium (15307-79-6) + silver nitrate → silver(I) diclofenac

Conditions	Yield
In water	87%
In methanol at 20℃; for 1h; Darkness;	85%
With ammonia In ethanol; water at 20℃; for 0.25h; pH=8;

isopropyloxycarbonyloxymethyl iodide (258841-42-8) + diclofenac sodium (15307-79-6) → 1-[(1-methylethoxy)carbonyloxy]methyl 2-[(2,6-dichlorophenyl)amino]phenylacetate (1264635-62-2)

Conditions	Yield
Stage #1: diclofenac sodium With sodium carbonate In N,N-dimethyl acetamide at 30℃; for 0.166667h; Inert atmosphere; Stage #2: isopropyloxycarbonyloxymethyl iodide In N,N-dimethyl acetamide at -10℃; for 0.75h; Inert atmosphere;	86.4%

trimethyltin(IV)chloride (1066-45-1) + diclofenac sodium (15307-79-6) → (CH3)3SnOC(O)CH2C6H4NHC6H3Cl2

Conditions	Yield
In chloroform byproducts: sodium chloride; under inert atmosphere; 1 equiv. of sodium salt of ligand refluxed withSn compd. in dry CHCl3 for 6-7 h; cooled to room temp.; filtered; solvent removed from filtrate by rotary evaporator; crystd. from CH2Cl2-hexane; elem. anal.;	86%

1-(2-aminoethyl)pyrrolidine (7154-73-6) + nickel(II) chloride hexahydrate + diclofenac sodium (15307-79-6) → [Ni(diclofenac)2(1-(2-aminoethyl)pyrrolidine)2] (1596252-87-7)

Conditions	Yield
Stage #1: nickel(II) chloride hexahydrate; diclofenac sodium In ethanol at 50℃; Stage #2: 1-(2-aminoethyl)pyrrolidine In ethanol at 20℃;	86%

diclofenac sodium (15307-79-6) + water (7732-18-5) + zinc(II) chloride (7646-85-7) → C28H24Cl4N2O6Zn

Conditions	Yield
In water at 20℃; for 3h;	86%

Upstream product

• 15362-40-0 1-(2,6-dichlorophenyl)indolin-2-one 
• 66156-75-0 2-(2-((2,6-dichlorophenyl)amino)phenyl)-2-oxoacetic acid 
• 100754-92-5 potassium 2-iodophenylacetate 
• 608-31-1 2,6-Dichloroaniline 
• 83281-93-0 N-(2,6-dichlorophenyl)-α-(methylthio)acetanilide 
• 83281-96-3 N-(2,6-dichlorophenyl)-α-(methylsulfinyl)acetanilide 
• 15308-01-7 2-chloro-N-(2',6'-dichlorophenyl)-N-phenylacetamide 
• 2444-36-2 2'-chloro-benzeneacetic acid 
• 71-36-3 butan-1-ol 
• 3559-26-0 (2-benzoylamino-phenyl)-acetic acid methyl ester 
• 30095-98-8 methyl (2-nitrophenyl)acetate 
• 101-41-7 benzeneacetic acid methyl ester 
• 35613-44-6 2-aminophenylacetic acid methyl ester 
• 15307-78-5 2-[(2,6-dichlorophenyl)amino]phenylacetic acid methyl ester 

Downstream Products

• 100499-89-6 aceclofenac benzyl ester 
• 134674-28-5 2-<(2,6-Dichlorphenyl)amino>phenylessigsaeure-(5-methyl-1,3-dioxolan-4-on-5-yl)ester 
• 134674-22-9 2-<(2,6-Dichlorphenyl)amino>phenylessigsaeure-(2,2-dimethyl-1,3-dioxolan-4-on-5-yl)ester 
• 134674-35-4 2-<(2,6-Dichlorphenyl)amino>phenylessigsaeure-(2,2,5-trimethyl-1,3-dioxolan-4-on-5-yl)ester 
• 15307-86-5 [2-(2,6-dichloroanilino)phenyl]acetic acid 
• 87906-12-5 1-O-<2-<(2,6-dichlorophenyl)amino>phenylacetyl>-2,3,4,6-tetra-O-acetyl-β-D-glucopyranose 
• 174316-61-1 2-(2,6-dichloroanilino)-5-nitrophenylacetic acid 
• 15362-40-0 1-(2,6-dichlorophenyl)indolin-2-one 
• 22121-58-0 2-[(2,6-dichlorophenyl)amino]benzaldehyde 
• 15307-78-5 2-[(2,6-dichlorophenyl)amino]phenylacetic acid methyl ester 
• 24542-74-3 1-(2,6-Dichlorphenyl)-2,3-indoldion 
• 27204-57-5 2-[(2,6-dichlorophenyl)amino]benzyl alcohol 
• 21789-10-6 [o-(2,6-dichloroanilino)-phenyl]-acetamide 
• 59-48-3 2-oxoindole 

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Relevant articles and documents

Synthesis method of diclofenac sodium

The invention discloses a synthesis method of diclofenac sodium, which comprises the following steps: (1) toluene. An oil layer is obtained by adding 2, 6 -dichlorophenol and sodium carbonate, keeping warm and refluxing, extracting the oil layer with water, and adding an alkali heat-preserving reaction in the oil layer to obtain 2, 6 -dichloroaniline. (2) 1, 2 Dichlorodimethylaniline prepared in step (6 -) is heated and melted, chloroacetyl chloride is added dropwise, and the heat is subjected to heat preservation reaction after being heated to crystallize to obtain N - (2, 6 - dichlorophenyl) - phenyl - chloroacetamide. (3) 2 (N - 2 Dichlorophenyl) 6 - phenyl - chloroacetamide prepared in step (-) is reacted with the aluminum trichloride to give a solid 1 - (2, 6 -dichlorophenyl) -2 -indolinone. (4) 3 (1 - 2-dichlorophenyl) 6 -indolinone prepared in step (-2 -) is added to alkali liquor, stirred and heated to reflux to obtain diclofenac sodium. The synthesis method is stable, easy to operate, low in cost, high in yield and suitable for industrial production.

Synthesis process of diclofenac sodium

The invention provides a synthesis process of diclofenac sodium, which is obtained by acylation reaction of o-aminobenzene acetate with 2 and 6 - dichlorophenoxy acetic acid respectively and acylation with chlorobenzoyl chloride followed by nucleophilic substitution with 2, 6 - dichlorophenol or 2 and 6 -dichlorophenol. Is hydrolyzed to give sodium diclofenac sodium. The synthesis process is simplified, the reaction condition is mild, and the yield and industrial popularization and application are facilitated.

Preparation method of 2-[(2, 6-dichlorophenyl) amino] sodium phenylacetate

The invention belongs to the field of chemical pharmacy, and relates to a production process of a chemical bulk drug, in particular to a preparation method of 2-[(2, 6-dichlorophenyl) amino] sodium phenylacetate. The preparation method comprises the following steps: taking 2, 6-dichlorodiphenylamine and chloroacetyl chloride as initial raw materials; and completing acylation reaction, Lewis acidicionic liquid catalyzed Friedel-Crafts alkylation reaction and hydrolysis reaction by a one-pot method to finally obtain the 2-[(2, 6-dichlorophenyl) amino] sodium phenylacetate. The 2-[(2,6-dichlorophenyl) amino] sodium phenylacetate is synthesized by adopting a one-pot preparation scheme, has the advantages of short reaction time, simplicity in operation, mild conditions, high yield, good catalytic effect, high selectivity, recyclability and the like, and is beneficial to industrial production.

Synthetic method of diclofenac sodium

The invention relates to a synthetic method of diclofenac sodium, and a synthetic route thereof, in a compound A, X is Cl, Br or I, M is Me, Et or Pro, a catalyst used for the condensation reaction isCuI, CuBr, CuBR2 or CuF2, and a sugar ligand used for the reaction is D-glucosamine hydrochloride, glucose, chitosan, D-galactose and L- arabinose. The method for synthesizing diclofenac sodium according to the invention has a purity of more than 98% and a total yield of two steps of up to 90% or more. According to the synthetic method of the diclofenac sodium, the purity of the product is up tomore than 98%, the total yield of two steps is up to more than 90%, and the yield is high; and D-glucosamine hydrochloride is adopted to replace ligands such as 8-hydroxyquinoline and the like which are high in price and large in environmental pollution, the pollution to the environment is reduced while the production cost is reduced.

A double-dispain preparation method

The invention discloses a method for preparing diclofenac sodium. The method is characterized by comprising the following steps of: obtaining N-chloro-N-(2,6-dichlorophenyl)phenylacetamide (III) through reacting a chloride reagent with N-(2,6-dichlorophenyl)phenylacetamide (IV); obtaining 1-(2,6-dichlorophenyl)-2-indolinone (II) through reacting N-chloro-N-(2,6-dichlorophenyl)phenylacetamide (III) with a certain amount of Lewis acid in an organic solvent; and finally obtaining diclofenac sodium (I) through enabling the 1-(2,6-dichlorophenyl)-2-indolinone (II) to be subjected to hydrolysis reaction in a sodium hydroxide solution. The method disclosed by the invention has the characteristics of simplicity in operation, easily-available reagents, low cost, mild conditions and the like, and provides a novel processing route for the synthesis of diclofenac sodium.

A General, Activator-Free Palladium-Catalyzed Synthesis of Arylacetic and Benzoic Acids from Formic Acid

A new catalyst for the carboxylative synthesis of arylacetic and benzoic acids using formic acid (HCOOH) as the CO surrogate was developed. In an improvement over previous work, CO is generated in situ without the need for any additional activators. Key to success was the use of a specific system consisting of palladium acetate and 1,2-bis((tert-butyl(2-pyridinyl)phosphinyl)methyl)benzene. The generality of this method is demonstrated by the synthesis of more than 30 carboxylic acids, including non-steroidal anti-inflammatory drugs (NSAIDs), under mild conditions in good yields.

Synthetic method of diclofenac sodium (by machine translation)

The invention belongs to the technical field of pharmaceutical chemical synthesis, specific non-steroidal anti-inflammatory analgesic synthetic method of diclofenac sodium. Synthetic method of this invention the reaction steps are as follows: by the phenylacetic acid nitration reaction layer which O-nitrophenyl acetate (2); by the compound (2) by hydrogenation reduction reaction O-amino acetate (3); by the compound (3) amino through amidation, to obtain 2 - (2 - benzamido-phenyl) acetate (4); by the compound (4) with thionyl chloride produce chlorinated imine intermediate, then under the action of the inorganic base with 2, 6 - dichlorophenol condensation preparation (E) - Methyl - 2 - (2 - ((2, 6 - dichloro phenoxy) (phenyl) methylene amino) phenyl) ester (5); by the compound (5) by the Chapman rearrangement reaction for preparing methyl 2 - (2 - (N- (2, 6 - Dichlorophenyl) benzoyl amino) phenyl) ester (6); by the compound (6) by hydrolysis to prepare diclofenac sodium. Benzene acetic acid methyl ester calculation, the overall yield is 67%. The method of the invention raw materials are easy, economic cost, simple operation, mild reaction conditions, the industrial production is easy. (by machine translation)

PROCESS FOR THE PREPARATION OF DICLOFENAC EPOLAMINE

The present invention concerns a process for the preparation of the salt diclofenac epolamine comprising the following steps: a) reacting 1 -(2,6-dichlorophenyl)-2-indolinone with a base selected from sodium hydroxide or potassium hydroxide in an aqueous solvent, thus obtaining sodium or potassium diclofenac salt; b) dissolving the so obtained sodium or potassium diclofenac salt in a solvent- mixture comprising water and an organic solvent selected from the group consisting of ethyl acetate, methyl isobutyl ketone, toluene, isobutyl acetate, n-butyl acetate, n-propyl acetate, isopropyl acetate; c) adding a strong acid to give diclofenac acid and removing the water phase; d) anhydrifying the remaining organic solvent phase; and e) adding 1-(2-hydroxyethyl)-pyrrolidine.

A method of producing fast dissolving tablets

A method of producing a fast-melt tablet comprises the steps of forming a mixture of components, the mixture comprising at least one fast dissolving sugar alcohol, at least one disintegrant or osmotic agent, and at least one an active component, blending the mixture for a period of time, and directly compressing the blended mixture at a compression force of typically between 5 and 20kN to form the fast-melt tablet. The process of the invention does not involve any granulation step, thereby making the process more energy efficient and cost effective. The fast dissolving sugar alcohol is selected from the group comprising: mannitol; sorbitol; erythritol; xylitol; lactose; dextrose; and sucrose, and comprises at least 50%, preferably at least 60%, and more preferably at least 70%, of the tablet (w/w). The active component is suitably provided in the form of microparticles or microcapsules having an average diameter of less than 125 microns. Also described are directly compressed fast dissolving type tablets obtainable by the process of the invention.

DELAYED TOTAL RELEASE TWO PULSE GASTROINTESTINAL DRUG DELIVERY SYSTEM

A two pulse gastrointestinal delivery system is provided. The system comprises a desired agent in combination with a swellable core material, the core being surrounded by an inner coat of a water-insoluble or relatively water-insoluble coating material in which particulate water-insoluble material is embedded. The inner coat is additionally surrounded by an outer coat that contains additional amounts of the desired agent. When the delivery device enters the gastrointestinal tract, the outer coat releases the desired agent contained therein and disintegrates, exposing the inner coat. The particulate matter in the inner coat takes up liquid, thus forming channels interconnecting the drug-containing core with the outside of the delivery device. Through these channels liquid enters the core which then swells to the point at which the inner coat is broken. When the integrity of the inner coat is destroyed, the core then disintegrates, immediately releasing all or most of the drug at a specific site. By controlling parameters in the device, such as the core material, carrier material in the coating, and particulate matter, the location of release of both pulses of the drug can be carefully controlled. The invention is also directed to a method of using the device for the treatment of disease by the release of drugs in the gastrointestinal tract in a location- and time-dependent manner.