- Synthesis method of diclofenac sodium
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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.
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- Synthesis process of diclofenac sodium
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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.
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Paragraph 0084-0087
(2021/09/26)
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- Preparation method of 2-[(2, 6-dichlorophenyl) amino] sodium phenylacetate
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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.
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- Synthetic method of diclofenac sodium
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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.
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Paragraph 0017-0026
(2019/04/26)
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- Synthetic method of diclofenac sodium (by machine translation)
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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)
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- A double-dispain preparation method
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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.
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- A General, Activator-Free Palladium-Catalyzed Synthesis of Arylacetic and Benzoic Acids from Formic Acid
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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.
- Wang, Lin,Neumann, Helfried,Beller, Matthias
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supporting information
p. 6910 - 6914
(2018/06/04)
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- PROCESS FOR THE PREPARATION OF DICLOFENAC EPOLAMINE
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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.
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Page/Page column 5
(2010/08/05)
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- A method of producing fast dissolving tablets
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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.
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- DELAYED TOTAL RELEASE TWO PULSE GASTROINTESTINAL DRUG DELIVERY SYSTEM
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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.
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- Pharmaceutical composition for ophthalmic use comprising a nonsteroidal anti-inflammatory and a decongestant drug
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A pharmaceutical aqueous solution for ophthalmic use comprising a nonsteroidal anti-inflammatory drug, having a carboxylic group, a decongestant drug and a mixture of a polysorbate and a poloxamer.
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- Gastric preparation with sustained release
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A gastric preparation developed in order to solve the technical problems of conventional preparations, which is prepared by the bilayer packing technique and comprises 5 to 60%, desirably 10 to 40% of a rapid release portion which can establish the therapeutic level of a drug shortly after the administration and 95 to 40%, desirably 90 to 60% of a sustained release portion which has a specific gravity or 1 or less and can maintain a satisfactory release rate.
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- Pharmaceutical composition for ophthalmic use comprising a nonsteroidal anti-inflammatory and a decongestant drug
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A pharmaceutical aqueous solution for ophthalmic use comprising a nonsteroidal anti-inflammatory drug, having a carboxylic group, a decongestant drug and a mixture of a polysorbate and a poloxamer.
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- Diclofenac sodium plaster
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A diclofenac sodium plaster has a backing material and a paste spread on the backing material. The paste is composed of diclofenac sodium, a penetration enhancer composed of 1-menthol and propylene glycol, and a hydrophilic base composed principally of a water-soluble polymer.
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- Synthesis and quantitative structure-activity relationships of diclofenac analogues
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The synthesis of a series of 2-anilinophenylacetic acid, close analogues of diclofenac, is described. These compounds were tested in two models used for evaluating the activity of nonsteroidal antiinflammatory drugs (NSAID's), inhibition of cyclooxygenase enzyme activity in vitro, and adjuvant-induced arthritis (AdA) in rats. Statistically significant correlations were found between the inhibitory activities of the compounds in these two models, indicating that cyclooxygenase inhibition seems to be the underlying mechanism for the antiinflammatory activity of these compounds. Quantitative structure-activity relationship (QSAR) analysis revealed that the crucial parameters for activity in both models were the lipophilicity and the angle of twist between the two phenyl rings. Optimal activities were associated with halogen or alkyl substituents in both ortho positions of the anilino ring. Compounds with OH groups in addition to two ortho substituents or compounds with only one or no ortho substituents were less active.
- Moser,Sallmann,Wiesenberg
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p. 2358 - 2368
(2007/10/02)
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- Formulation with special 1,2-diacylglycero-3-phosphocholines for the treatment of gastrointestinal disorders
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Pharmaceutical formulations for the treatment of gastrointestinal disorders, which contain as the active component an effective gastrointestinal disorder alleviating amount of a 1,2-diacylglycero-3-phosphocholine in which 75-86% by weight of the acyl radicals are unsaturated fatty acid radicals having a chain length of 16, 18 or 20 carbon atoms. The mixtures of fatty acid radicals in the acyl groups in the 1- and 2-positions preferably have different compositions. The formulations can also contain other active compounds, in particular those which display injurious gastrointestinal side effects.
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- Sprayable pharmaceutical composition for topical use
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Sprayable pharmaceutical preparations with an arylalkanoic acid or its salts as the active agent, suitable for topical application, containing as solvent a mixture of one or more volatile solvents and one or more non-volatile solvents in the weight ratio range of 1:1 to 20:1. They are especially suitable for the treatment of traumatic and rheumatic diseases.
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- Process for production of o-(2,6-dichloroanilino)-phenylacetic acid
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There is provided a process for production of o-(2,6-dichloroanilino)phenylacetic acid or a salt thereof by reacting o-chlorophenylacetic acid or an alkali metal salt thereof with 2,6-dichloroaniline in the presence of a base and at least 0.5 mol of a copper catalyst per mol of o-chlorophenylacetic acid in a polar solvent.
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- Process for preparation of o-(2,6-dichloroanilino)phenylacetic acid and novel intermediate for use in preparation of the same
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Disclosed is a process for the preparation of o-(2,6-dichloroanilino)phenylacetic acid (Diclofenac) or its pharmacologically acceptable acid addition salt, which comprises hydrolyzing an N,N-disubstituted-o-(2,6-dichloroanilino)phenylacetamide derivative with an alkali. Also a novel intermediate for use in the preparation of Diclofenac, that is, an N,N-disubstituted-o-halogenophenylacetamide in which the halogen is iodine or bromine, is disclosed.
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