- Preparation method of olopatadine hydrochloride
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The method comprises the following steps: [3 - (dimethylamino) propyl] triphenylphosphonium bromide hydrobromide is added into tetrahydrofuran. The sodium hydride and dimethyl sulfoxide are added 11 - oxo -6, 11 - dihydrodibenzo [b, e] oxazepine -2 - acetic acid and stirred until the reaction system forms a black brown suspension reaction. The reaction solution is quenched by a mixed solution of purified water and tetrahydrofuran, and then the aqueous phase is treated with a mixed solvent of hydrochloric acid and n-butanol. The olopatadine hydrochloride is stirred and added with hydrochloric acid to form a white turbid liquid, and then is filtered through stirring after stirring, and is dried to obtain olopatadine hydrochloride, and the prepared oxalolopatadine hydrochloride is high in yield and short in reaction route.
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Paragraph 0039; 0044-0045
(2021/11/10)
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- A preparation method of olopatadine hydrochloride (by machine translation)
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The invention discloses a method for preparation of olopatadine hydrochloride, comprises the following steps: preparation of olopatadine hydrochloride crude; preparation of olopatadine free alkali; of olopatadine hydrochloride. The invention key steps upgraded, has the following advantages: 1, thereby reducing the reaction steps, the loss is reduced, thereby improving the production efficiency; 2, reduces the generation of hydrogen gas, decreasing the potential safety hazard 3, reduces the processing difficulty at the same time guarantee quality and yield unchanged; 4, optimizing the reaction temperature, pick out the low-temperature harsh reaction, reducing the reliance on the equipment; 5, in addition to eliminating the original separate heterogeneous step; 6, high yield and quality. (by machine translation)
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Paragraph 0012; 0023
(2019/10/29)
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- Preparation technique of olopatadine hydrochloride
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The invention relates to a preparation technique of olopatadine hydrochloride. The technique comprises the following steps: carrying out reaction on 2-(chloromethyl)benzoic acid and p-hydroxyphenylacetic acid to generate Isoxepac, and carrying out reaction on the Isoxepac and a Wittig-horner agent generated by N,N-dimethylaminochloropropane hydrochloride to generate hydrochloride, thereby obtaining the olopatadine hydrochloride. The method uses the low-cost raw materials for reaction, avoids using toxic agents in the reaction process, has the advantages of short process route, mild reaction conditions, controllable operation, short production cycle, low energy consumption, high yield, high purity and safe technique, and is suitable for industrial production.
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Paragraph 0056; 0057
(2016/10/27)
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- A process for the preparation of olopatadine hydrochloride
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The invention relates to a method for preparing a compound, namely, olopatadine hydrochloride. The method specifically comprises the following steps: by taking 2-chloromethyl methyl benzoate and methyl 4-hydroxyphenylacetate as initial raw materials, performing etherification, hydrolysis and cyclization, further performing wittig reaction, and salifying, thereby synthesizing olopatadine hydrochloride. The process is gentle in process reaction condition, acetic anhydride is adopted to replace polyphosphoric acid, a hydrochloric acid organic solvent is adopted to effectively split Z/E type olopatadine so as to obtain olopatadine hydrochloride, conversion of Z/E configuration is effectively achieved after an E configuration byproduct is treated by using concentrated hydrochloric acid, the yield of olopatadine hydrochloride is increased, the product purity is good, and the feasibility of industrialization production is greatly improved.
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- A PROCESS FOR THE PREPARATION OF OLOPATADINE AND SYLIL INTERMEDIATES THEREOF
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The present invention refers to a new "one-pot" process for the preparation of olopatadine via intermediates of formula (III).
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Paragraph 7; 8
(2015/05/19)
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- A PROCESS FOR THE SYNTHESIS OF OLOPATADINE
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The present invention provides a process for the synthesis of olopatadine. Further, the invention discloses a process that results in improved yield of the desired Z isomer.
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- Stereoselective syntheses of the antihistaminic drug olopatadine and its E-isomer
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Practical stereoselective synthetic routes to the antihistaminic drug olopatadine and its E-isomer have been developed, the key steps being a trans stereoselective Wittig olefination using a nonstabilized phosphorus ylide and a stereoselective Heck cyclization. The stereoselectivity of the Wittig reaction depends on both the phosphonium salt anion and the cation present in the base used to generate the ylide.
- Bosch, Joan,Bachs, Jordi,Gomez, Antonia M.,Griera, Rosa,Ecija, Marta,Amat, Mercedes
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p. 6340 - 6344
(2012/10/07)
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- A new efficient synthetic route for the synthesis of the antiallergic drug, olopatadine hydrochloride, via stereospecific palladium-catalyzed reaction
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A new practical and efficient synthetic route for the synthesis of olopatadine hydrochloride via the intramolecular stereospecific seven-membered ring cyclization from an alkyne intermediate using palladium catalyst and hydride source was established. Furthermore, the optimization of that key stereospecific reaction was examined by design of experiment (DoE), and the desired Z-isomer could be obtained with high yield.
- Nishimura, Koichiro,Kinugawa, Masahiko
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p. 225 - 231
(2012/06/05)
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- PROCESS FOR PRODUCING DIBENZOXEPIN COMPOUND
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A process for producing (Z)-11-(3-dimethylaminopropylidene)-6,11-dihydrodibenz[b,e]oxepin-2-acetic acid or an acid addition salt thereof, which comprises subjecting 11-hydroxy-11- (3-dimethylaminopropyl)-6,11-dihydrodibenz[b,e] oxepin-2-acetic acid or a salt thereof to a heat treatment in a solvent and a water removal treatment in a reaction system in the presence of an acid selected from a group consisting of hydrogen chloride, sulfuric acid, methanesulfonic acid and p-toluenesulfonic acid, enables the production of (Z)-11-(3-dimethylamino-oropylidene)-6,11-dihydrodibenz[b,e]oxepin-2-acetic acid or an acid addition salt thereof, which is useful as a medicinal agent, in a high yield and in an industrially advantageous manner.
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Page/Page column 6
(2011/11/13)
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- IMPROVED PROCESS FOR LL-[(Z)-3-(DIMETHYLAMINO)PROPYIIDENEL-6-LL- DIHYDRODIBENZ[B,EL OXEPIN-2-ACETICACID
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The present invention relates to an improved process for the preparation of 11- [(Z)-3-(dimethylamino)propylidene]-6, 11 -dihydrodibenzo[b,e]oxepin-2-aceticacid compound of formula- 1 and its pharmaceutically acceptable salts.
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Page/Page column 20
(2011/11/01)
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- PROCESS FOR PREPARATION OF OLOPATADINE HYDROCHLORIDE
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Disclosed here is a process for preparation of compound 11 - (Z) - [3 - (Dimethylamino) propylidene] - 6, 11 - dihydrodibenz [b, e] oxepin -2 - yl - acetic acid (Olopatadine) and its pharmaceutically acceptable salt comprising reacting compound of Formula (XII) where R1 and R2 independently represent H, or C1 - C4 alkyl group; with 3-dimethylaminopropyl magnesium halide of Formula (XIII) where X is Chlorine, bromine or iodine.
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- CRYSTALLINE POLYMORPHIC FORMS OF OLOPATADINE HYDROCHLORIDE AND PROCESSES FOR THEIR PREPARATION
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The invention relates to new polymorphic forms of olopatadine hydrochloride, designated herein as olopatadine hydrochloride Forms A and B, and methods of preparing, purifying and treating them.
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Page/Page column 6
(2010/06/16)
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- Process for obtaining olopatadine and intermediates
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Olopatadine can be obtained by means of a process comprising hydrolysis of a compound of general formula (II), wherein Y is OR1, wherein R1 is C1-C7 alkyl, C3-C7 cycloalkyl, aryl, or heterocycle; or NR2R3, wherein R2 and R3, independently from each other, are C1-C7 alkyl, aryl, or R2 and R3 together with the nitrogen atom to which they are bound form a heterocycle of 3 to 7 members, obtained by means of a process comprising reacting the corresponding ester or amide of 6,11-dihydro-11-oxodibenz[b,e]oxepin-2-acetic acid with a suitable Witting reagent, in the presence of a base in a reaction medium comprising an organic solvent.
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Page/Page column 14
(2010/02/17)
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- PROCESS FOR THE PREPARATION OF OLOPATADINE
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The present invention relates to a novel process for the preparation of olopatadine hydrochloride starting from an advanced intermediate.
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Page/Page column 27-28
(2010/11/05)
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- PROCESS FOR PREPARATION OF OLOPAT ADINE HYDROCHLORIDE
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Disclosed herein is a process for preparation of compound 11 - (Z) - [3 - (Dimethylamino) propylidene] - 6, 11 - dihydrodibenz [b, e] oxepin -2 - yl - acetic acid (Olopatadine) and its pharmaceutically acceptable salt; comprising reacting carboxylic acid protected 11 - oxo - 6, 11 - Dihydrodibenz [b, e] oxepin - 2 - acetic acid with 3 - dimethylaminopropyl triphenyl phosphonium halide in presence of a suitable base and an organic solvent.
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Page/Page column 11-12
(2009/07/25)
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- Process for the preparation of (Z)-[11-(3-dimethylamino-propyliden)-6,11-dihydro-dibenzo[b,e]oxepin-2-yl]-acetic acid hydrochloride
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The present invention relates an optimised process for the preparation of the compound of formula (Z)-[11-(3-dimethylamino-propyliden)-6,11-dihydro-dibenzo[b,e]oxepin-2-yl]-acetic acid hydrochloride in a higher purity, which comprises the preparation of salts of advanced intermediates and final crystallization of compound of formula 11-[(Z)-3-(dimethylamino)propylidene]-6,11-dihydro-dibenz[b,e]oxepin-2-yl]-acetic acid hydrochloride.
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Page/Page column 6
(2010/11/30)
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- Polymorphic forms of olopatadine hydrochloride and methods for producing olopatadine and salts thereof
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The present invention provides a novel polymorphic form of olopatadine hydrochloride ([(Z)-3-(dimethylamino)propylidene]-6,11-dihydrodibenz[b,e]oxepin-2-acetic acid hydrochloride), a selective histamine H1-receptor antagonist that is used for the treatment of ocular symptoms of seasonal allergic conjunctivitis. The present invention also provides novel methods for producing olopatadine on a large scale, and in a manner that is cost effective, provides a low level of impurities and eliminates the need to use the costly and dangerous base, butyllithium, which is used in prior art reactions for making olopatadine. The present invention further provides novel processes for carrying out a large scale production of 3-dimethylaminopropyltriphenylphosphonium bromide and its corresponding hydrobromide salt, which are employed in the production of olopatadine, and pharmaceutically acceptable salts of olopatadine.
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Page/Page column 21
(2008/06/13)
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- PROCESS FOR THE PREPARATION OF 11-[(Z)-3-(DIMETHYLAMINO)PROPYLIDENE]-6,11-DIHYDRO-DIBENZ[B,E]OXEPIN-2-YL]-ACETIC ACID
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Process for the preparation of olopatadine (I), which comprises reacting a compound of formula (V) in the presence of a palladium catalyst to provide a compound of formula (VI), wherein the acid protecting group is removed to provide the compound of formula (I) and if desired, transformation into its salts.
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Page/Page column 15
(2008/06/13)
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