- An improved process for the preparation of highly pure solifenacin succinate via resolution through diastereomeric crystallisation
-
An improved process for the preparation of solifenacin succinate (1) involving resolution through diastereomeric crystallization is described. (1S)-IQL derivative (5) is esterified to form (1S)-ethoxycarbonyl IQL derivative (6) which is condensed with (RS)-3-quinuclidinol (7) to form a solifenacin diastereomeric mixture (8); this is subjected to resolution through diastereomeric crystallization to produce solifenacin succinate (1), which is used for the treatment of an overactive bladder.
- Trinadhachari, Ganala Naga,Kamat, Anand Gopalkrishna,Venkata Balaji, Boddu,Prabahar, Koilpillai Joseph,Naidu, Kolukuluru Mohan,Babu, Korupolu Raghu,Sanasi, Paul Douglas
-
p. 934 - 940
(2014/10/15)
-
- NOVEL PROCESS FOR THE PREPARATION OF SOLIFENACIN SUCCINATE
-
The present invention relates to a process for the preparation of Solifenacin succinate by condensing a compound of formula (IVb) with (RS)-3-quinuclidinol, wherein, R represents methyl, ethyl, isopropyl; to produce a diastereomeric mixture of (1S)-3,4-dihydro-1-phenyl-2(1H)-isoquinolinecarboxylic acid (3RS)-1-azabicyclo[2.2.2]oct-3-yl ester, which is treated with succinic acid in a solvent or mixture of solvents to produce optically pure Solifenacin succinate, Formula (X).
- -
-
Paragraph 0034; 0035; 0036
(2013/05/22)
-
- NOVEL PROCESS FOR THE PREPARATION OF SOLIFENACIN SUCCINATE
-
The present invention relates to a process for the preparation of Solifenacin succinate by condensing a compound of formula (IVb) with (RS)-3-quinuclidinol, wherein, R represents methyl, ethyl, isopropyl; to produce a diastereomeric mixture of ( 1S)-3,4-dihydro- 1 -phenyl-2( 1 H)-isoquinolinecarboxylic acid (3RS)- 1 - azabicyclo[2.2.2]oct-3-yl ester, which is treated with succinic acid in a solvent or mixture of solvents to produce optically pure Solifenacin succinate, Formula (X).
- -
-
-
- Efficient and single pot process for the preparation of enantiomerically pure solifenacin succinate, an antimuscarinic agent
-
The development of an efficient and economic one-pot process, in which the configuration of the chiral centers of the starting materials is retained, for the preparation of highly pure solifenacin succinate, an antimuscarinic agent, is presented in this communication. The earlier reported processes suffer from the drawbacks of racemization and low yields due to the use of strong base, higher temperatures, and longer reaction times. The present work circumvents these issues by activating (3R)-quinuclidin-3-ol into a mixed active carbonate derivative by treating it with bis(4-nitrophenyl)carbonate. The subsequent reaction of the active carbonate with an enantiomerically pure amine without using any base at ambient temperature provided enantiomerically pure solifenacin with an overall yield of 90%. Graphical Abstract: [Figure not available: see fulltext.]
- Niphade, Navnath C.,Jagtap, Kunal M.,Mali, Anil C.,Solanki, Pavankumar V.,Jachak, Madhukar N.,Mathad, Vijayavitthal T.
-
body text
p. 1181 - 1186
(2012/01/06)
-
- PROCESS FOR THE PREPARATION OF SOLIFENACIN
-
A process for the preparation of (1S)-QR)-I -azabicyclo[2.2.2.]oct-3-yl 3,4-dihydro-1-phenyl- 2(1H)-isoquino-line carboxylate by reacting (1S)-alkyl 1-phenyl-1,2,3,4-tetrahydro-2-isoquinoline carboxylate with 3-(R)-quinuclidol in an inert solvent, where a primary alkyl ester of the carboxylate whose alkyl length is C1-C4 is used and the reaction is catalyzed by a non-nu-cleophilic base.
- -
-
Page/Page column 3
(2009/08/18)
-
- A METHOD FOR THE PREPARATION OF SOLIFENACIN
-
A method of preparing (lS)-(3R)-l-azabicyclo[2.2.2]oct-3-yl 3,4-dihydro-l-phenyl-2(lH)- isoquinoline carboxylate (solifenacin) or its pharmaceutically acceptable salts with high optic purity, wherein the crude solifenacin base is transformed to the hydrogen tartrate, which is then optionally transformed to another pharmaceutically acceptable salt or the base of solifenacin. A crystalline salt of solifenacin hydrogen tartrate.
- -
-
Page/Page column 5
(2008/12/06)
-
- PROCESS FOR PREPARING SOLIFENACIN AND ITS SALTS
-
The present invention relates to solifenacin in solid form and a process for its preparation and to a process for the preparation of (1S)-1-Phenyl-1,2,3,4-tetrahydro-isoquinoline, a key intermediate in the synthesis of solifenacin and its salts.
- -
-
Page/Page column 22; 23
(2008/06/13)
-
- COMPOSITION CONTAINING SOLIFENACIN SUCCINATE
-
A solifenacin succinate-containing composition with less impurities which can be used as a bulk for pharmaceutical is provided. The solifenacin succinate-containing compostiion of the present invention has a reduced content of especially its optical isomers in comparison with the known compositions containing an acid addition salt of solifenacin, so that it can be used for production of a therapeutic agent containing solifenacin succinate. In addition, the above-described solifenacin succinate-containing composition can be easily produced in accordance with the production method of the present invention.
- -
-
Page/Page column 9; 10
(2008/06/13)
-
- Synthesis and antimuscarinic properties of quinuclidin-3-yl 1,2,3,4-tetrahydroisoquinoline-2-carboxylate derivatives as novel muscarinic receptor antagonists
-
In the course of continuing efforts to develop potent and bladder-selective muscarinic M3 receptor antagonists, quinuclidin-3-yl 1-aryl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate derivatives and related compounds were designed as conformationally restricted analogues of quinuclidin-3-yl benzhydrylcarbamate (8). Binding assays with rat muscarinic receptor subtypes revealed that the quinuclidin-3-yl 1-aryl-1,2,3,4- tetrahydroisoquinoline-2-carboxylate derivatives showed high affinities for the M3 receptor, and selectivity for the M3 receptor over the M2 receptor. Of these derivatives, (+)-(1S,3'R)-quinuclidin-3'-yl 1-phenyl-l,2,3,4-tetrahydroisoquinoline-2-carboxylate monohydrochloride (9b) exhibited almost the same inhibitory activity against bladder contraction to that of oxybutynin (1), and more than 10-fold selectivity for bladder contraction versus salivary secretion, demonstrating that 9b may be useful for the treatment of symptoms associated with overactive bladder without having side effects such as dry mouth.
- Naito, Ryo,Yonetoku, Yasuhiro,Okamoto, Yoshinori,Toyoshima, Akira,Ikeda, Ken,Takeuchi, Makoto
-
p. 6597 - 6606
(2007/10/03)
-