Physical Resolution Patents (Class 562/402)
  • Patent number: 10765968
    Abstract: Provided is a supercritical fluid chromatography method, system, and components comprising such a system wherein a non-polar solvent may replace a portion or all of a polar solvent for the purpose of separating or extracting desired sample molecules from a combined sample/solvent stream. The method and system are designed to eliminate or reduce the amount of polar solvent necessary for chromatographic separation and/or extraction of desired samples to less than or equal to twenty percent polar solvent within the total volume concentration of the total solvents used, and the technique may include one or more of a supercritical fluid chiller, a supercritical fluid pressure-equalizing vessel, and a supercritical fluid cyclonic separator. The supercritical fluid chiller and the use of the chiller allow efficient and consistent pumping of liquid-phase gases employing off-the-shelf HPLC pumps in the supercritical chromatography system using liquid-phase gas mobile phase.
    Type: Grant
    Filed: January 3, 2017
    Date of Patent: September 8, 2020
    Inventors: Kenneth Joseph James, Brian Jeffrey Waibel, Kenneth Richard Krewson, Curtis Ebersold, Kim Ferrara
  • Patent number: 10251854
    Abstract: Disclosed are an S-(carboxymethyl)-cysteine pharmaceutical compound (I), and a preparation method and use thereof. Also disclosed are an S-(carboxymethyl)-D-cysteine ammonium salt monohydrate, and use thereof in preparation of medicines for preventing and treating respiratory system diseases such as chronic obstructive pulmonary diseases, in particular in preparation of expectorants. The compounds can reduce airway resistance and production of oxides in rat COPD models, increase the level of antioxidants, and alleviate damage caused by the oxides and inflammatory mediators to lungs.
    Type: Grant
    Filed: July 5, 2013
    Date of Patent: April 9, 2019
    Assignees: Guangzhou Baiyunshan Pharmaceutical Holdings Co., Ltd., Baiyunshan Pharmaceutical General Factroy Guangzhou Institute of Respiratory Disease
    Inventors: Mao Chen, Shaoxuan Zhu, Ping Wan, Wei Wang, Wei Liao, Hairong Hu, Xianglin Fu, Jin Feng, Binge Huang, Lin Zhang, Nanshan Zhong, Jinping Zheng, Hongying Mo
  • Patent number: 9181181
    Abstract: The present invention relates to 2-(substituted sulphur, sulphone or sulphoxide)-3-(substituted phenyl)propionic acid derivatives, 2-(substituted oxygen)-3-(substituted phenyl)propionic acid derivatives, benzoic acid derivatives, and derivatives of 2-methyl-2-(phenoxy or phenylthio)propanoic acid and 2-(methyl or ethyl)-2-(phenoxy or phenylthio)butanoic acid, to processes for preparing such compounds, to their use in the treatment of inflammatory conditions, and to pharmaceutical compositions containing them.
    Type: Grant
    Filed: June 11, 2014
    Date of Patent: November 10, 2015
    Assignee: Albireo AB
    Inventors: Anders Broo, Johan Gottfries, Michael Kossenjans, Li Lanna, Eva-Lotte Lindstedt-Alstermark, Kristina A. Nilsson, Bengt Ohlsson, Maria Thorstensson, Maria Boije
  • Patent number: 8992783
    Abstract: Method for enantioseparation of a chiral system with compound formation comprising a pair of enantiomers. The method comprises the steps of: placing the chiral system to be processed, which is optically enriched by a target enantiomer, in the 3-phase region of the ternary phase diagram of chiral compound forming systems to achieve the establishment of the solid/liquid phase equilibria; phase-separating the liquid and solid phase formed by the placing step; shifting the eutectic composition of the remaining liquid towards a lower eutectic composition (xE) until the overall composition is located in the 2-phase region of the ternary phase diagram of chiral compound forming systems; and performing crystallization in the 2-phase region of the ternary phase diagram for obtaining the target enantiomer in the solid phase. In some cases the shifting step can be skipped.
    Type: Grant
    Filed: June 18, 2009
    Date of Patent: March 31, 2015
    Assignee: Max-Planck-Gessellschaft zur Förderung der Wissenschaften e.V.
    Inventors: Heike Lorenz, Henning Kaemmerer, Daniel Polenske, Andreas Seidel-Morgenstern
  • Publication number: 20150005530
    Abstract: The present invention provides a L-enantiomers selective composite membrane useful for separation of optical isomers and the process for the preparation thereof. The invention further provides a membrane based pressure driven separation process for separation of enantiomers from their mixture to obtain optical pure isomers. The present invention also provides a membrane based method for optical resolution of racemic mixtures of amino acids to obtain optically pure amino acids.
    Type: Application
    Filed: February 6, 2013
    Publication date: January 1, 2015
    Inventors: Kripal Singh, Hari Chand Bajaj, Pravin Ganeshrao Ingole
  • Patent number: 8835676
    Abstract: Enantiomerically pure L-tert-leucine and D-tert-leucine were prepared from (DL)-tert-leucine by diastereomeric salt formation using dibenzoyl-d-tartaric acid as the resolving agent.
    Type: Grant
    Filed: June 7, 2011
    Date of Patent: September 16, 2014
    Assignee: Divi's Laboratories Ltd.
    Inventors: Murali Krishna Prasad Divi, Gundu Rao Padakandla, Mysore Aswatha Narayana Rao, Shaik Nowshuddin
  • Patent number: 8822721
    Abstract: The invention concerns a method for separating a racemic compound-forming chiral substance by a cyclic crystallization process which is conducted in at least one first crystallization unit (10) and in at least one second crystallization unit (18), wherein in a first process cycle an enantiomer is crystallized in the first crystallization unit (10) and a racemic compound is crystallized in the second crystallization unit (18), wherein in a second process cycle the enantiomer is crystallized in the second crystallization unit (18) and the racemic compound is crystallized in the first crystallization unit (10), wherein during each process cycle in at least one process sub-step (B?C, F?G) a mother liquor (12) being contained in the first crystallization unit (10) is mutually exchanged with a mother liquor (20) being contained in the second crystallization unit (18). An auto-seeding process sub-step is applied at the beginning of a process cycle.
    Type: Grant
    Filed: February 8, 2012
    Date of Patent: September 2, 2014
    Assignee: Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V.
    Inventors: Heike Lorenz, Daniel Polenske, Linzhu Klukas, Andreas Seidel-Morgenstern
  • Patent number: 8604237
    Abstract: Subject of the invention is a method for the production of L-carnitine, comprising the steps of (a) providing a solution comprising at least 5% (w/w) carnitine in a first solvent, wherein the carnitine is a mixture of D- and L-carnitine, (b) optionally seeding the solution with L-carnitine crystals, (c) adding an second solvent, in which the L-carnitine is not soluble or has a low solubility, (d) isolating crystals comprising L-carnitine.
    Type: Grant
    Filed: November 15, 2010
    Date of Patent: December 10, 2013
    Assignee: Lonza Ltd
    Inventors: Thomas Büchner, Gesa Paradies
  • Publication number: 20130184489
    Abstract: The invention concerns a method for separating a racemic compound-forming chiral substance by a cyclic crystallization process which is conducted in at least one first crystallization unit (10) and in at least one second crystallization unit (18), wherein in a first process cycle an enantiomer is crystallized in the first crystallization unit (10) and a racemic compound is crystallized in the second crystallization unit (18), wherein in a second process cycle the enantiomer is crystallized in the second crystallization unit (18) and the racemic compound is crystallized in the first crystallization unit (10), wherein during each process cycle in at least one process sub-step (B?C, F?G) a mother liquor (12) being contained in the first crystallization unit (10) is mutually exchanged with a mother liquor (20) being contained in the second crystallization unit (18). An auto-seeding process sub-step is applied at the beginning of a process cycle.
    Type: Application
    Filed: February 8, 2012
    Publication date: July 18, 2013
    Applicant: Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V.
    Inventors: Heike LORENZ, Daniel POLENSKE, Linzhu KLUKAS, Andreas SEIDEL-MORGENSTERN
  • Patent number: 8324425
    Abstract: Methods for producing compounds having activity as an ?2? ligand are provided.
    Type: Grant
    Filed: September 23, 2011
    Date of Patent: December 4, 2012
    Assignee: Daiichi Sankyo Company, Limited
    Inventors: Yutaka Kitagawa, Makoto Imai
  • Publication number: 20120259127
    Abstract: A process for the resolution of two enantiomers which involves inducing the preferential crystallization of one enantiomer by adjusting the composition of a suspension or solution including a racemic mixture of the two enantiomers and a solvent, by evaporation of the latter.
    Type: Application
    Filed: December 16, 2010
    Publication date: October 11, 2012
    Applicant: UNIVERSITE DE ROUEN
    Inventors: Gerard Coquerel, Guillaume Levilain
  • Publication number: 20120245379
    Abstract: Enantiomerically pure L-tert-leucine and D-tert-leucine were prepared from (DL)-tert-leucine by diastereomeric salt formation using dibenzoyl-d-tartaric acid as the resolving agent.
    Type: Application
    Filed: June 7, 2011
    Publication date: September 27, 2012
    Applicant: DIVI'S LABORATORIES LIMITED
    Inventors: Murali Krishna Prasad Divi, Gundu Rao Padakandla, Mysore Aswatha Narayana Rao, Shaik Nowshuddin
  • Publication number: 20120197040
    Abstract: The invention concerns a method for separating a racemic compound-forming chiral substance by a cyclic crystallization process which is conducted in at least one first crystallization unit (10) and in at least one second crystallization unit (18), wherein in a first process cycle an enantiomer is crystallized in the first crystallization unit (10) and a racemic compound is crystallized in the second crystallization unit (18), wherein in a second process cycle the enantiomer is crystallized in the second crystallization unit (18) and the racemic compound is crystallized in the first crystallization unit (10), wherein during each process cycle in at least one process sub-step (B?C, F?G) a mother liquor (12) being contained in the first crystallization unit (10) is mutually exchanged with a mother liquor (20) being contained in the second crystallization unit (18). An auto-seeding process sub-step is applied at the beginning of a process cycle.
    Type: Application
    Filed: February 8, 2012
    Publication date: August 2, 2012
    Inventors: Heike LORENZ, Daniel POLENSKE, Linzhu KLUKAS, Andreas SEIDEL-MORGENSTERN
  • Publication number: 20120041225
    Abstract: The present invention provides a means for the rapid selection of optimum resolving agents and solvents, combinations and conditions to separate optical isomers. The present invention combinedly describes and automates a full lifecycle of chiral separation method development and optimization through a series of kits and procedures providing screening, automation for screening, racemate recovery, enantiomer preparation, and method optimization.
    Type: Application
    Filed: October 21, 2011
    Publication date: February 16, 2012
    Inventor: Niteen A. Vaidya
  • Patent number: 8076511
    Abstract: High yields and purity are obtained in the purification of enantiomers of chiral carboxylic acids by preparative-scale chromatography by including a tertiary alcohol in the mobile phase in conjunction with an acidic modifier and a hydrophobic solvent. The tertiary alcohol is superior to other, more commonly used alcohols by reducing the extent of esterification of the enantiomer that otherwise lowers the yield and the purity.
    Type: Grant
    Filed: May 18, 2007
    Date of Patent: December 13, 2011
    Assignee: Ampac Fine Chemicals LLC.
    Inventors: Der-Shing Huang, Olivier Dapremont, Patrick Berget, Xa Her, Darin Sanchez
  • Patent number: 7678938
    Abstract: The invention relates to pure (R)-CMH and to the optical resolution of CMH-racemate, a key intermediate in the synthesis of (S)-Pregabalin. The invention also relates to the process for optically purifying (R)-CMH and to the process for isolating (S)-CMH from the mother liquor.
    Type: Grant
    Filed: August 14, 2007
    Date of Patent: March 16, 2010
    Assignee: Teva Pharmaceutical Industries Ltd.
    Inventors: Lilach Hedvati, Ziv Dee-Noor, Claude Singer, Gideon Pilarski
  • Publication number: 20080207944
    Abstract: Methods for racemate separation for compound-forming substances. In this method, at least one fraction which is enriched with an enantiomer is produced in one method step. Finally, a preferred crystallization is carried out on the fraction.
    Type: Application
    Filed: August 17, 2006
    Publication date: August 28, 2008
    Applicant: Max-Planck-Gesellschaft Zur Forderung Der Wissenshaften E.V.
    Inventors: Andreas Seidel-Morgenstern, Heike Lorenz, Daniel Polenske
  • Patent number: 7321055
    Abstract: Optically active diphenylalanine compounds may be conveniently prepared in a good yield by reacting a diphenylalanine compound represented by formula (1) with an optically active amine compound represented by formula (2) in the presence of an organic solvent to give a diastereomeric salt represented by formula (5) and then treating the diastereomeric salt under acidic conditions to give an optically active diphenylalanine compound represented by formula (3): wherein each symbol is as defined in the specification.
    Type: Grant
    Filed: August 4, 2006
    Date of Patent: January 22, 2008
    Assignee: Ajinomoto Co., Inc.
    Inventors: Takayuki Hamada, Masayuki Oshita, Masanobu Yatagai
  • Patent number: 7214819
    Abstract: A method of obtaining an enantioenriched organic compound comprising the steps of: 1) generating from a starting racemic, non-enantiopure or achiral compound a first mixture comprising at least one fluorous-tagged compound and at least one other non-fluorous tagged compound, at least one of these two compounds being enantioenriched relative to the starting compound; 2) contacting a first non-fluorous phase including the first mixture with a fluorous phase at a first phase interface, the fluorous-tagged compound distributing between the first non-fluorous phase and the fluorous phase; and 3) contacting the fluorous phase with a second non-fluorous phase at a second phase interface. The method further includes the step of having a third compound in the second non-fluorous phase that reacts with the fluorous-tagged compound to produce a second compound and the step of generating the first mixture by chemical or enzymatic kinetic resolution of a racemic or non-enantiopure compound.
    Type: Grant
    Filed: May 21, 2003
    Date of Patent: May 8, 2007
    Assignee: Fluorous Technologies, Inc.
    Inventors: Dennis Patrick Curran, Zhiyong Luo
  • Patent number: 7214820
    Abstract: The present invention provides a method for producing optically active flurbiprofen. The method of the present invention includes mixing racemic flurbiprofen and (S)- or (R)-3-methyl-2-phenylbutylamine in an organic solvent to produce a diastereomeric salt; and treating the diastereomeric salt with an acid in a second solvent. In the method of the present invention, flurbiprofen having a desired absolute configuration can be obtained very efficiently without repeating the procedure for optical resolution a plurality of times.
    Type: Grant
    Filed: January 20, 2004
    Date of Patent: May 8, 2007
    Assignee: Nagase & Co., Ltd.
    Inventors: Shunji Kamiyama, Kazuto Yoshida, Yasuo Chikusa, Jun Matsumoto, Keisuke Matsuyama
  • Patent number: 7034178
    Abstract: This invention is drawn to a process for the production of (R,R)-phenylisoserine or a 1–4C-alkyl ester thereof.
    Type: Grant
    Filed: June 27, 2002
    Date of Patent: April 25, 2006
    Assignee: Altana Pharma AG
    Inventors: Wijnand Faber, Jan Koek, Jörg Senn-Bilfinger, Ton Vries
  • Patent number: 7019152
    Abstract: The present invention relates to the field of organic synthesis and more particularly to a new process for the optical resolution of a precursor of sclareolide. This process includes the reaction of [(1RS,2RS,4aSR,8aSR)-2-hydroxy-2,5,5,8a-tetramethyldecahydronaphthalen-1-yl]acetic acid, or an alkaline salt thereof, with an enantiomer of the 2-(methylamino)-1-phenyl-1-propanol, or an ammonium salt thereof respectively, which is used as resolving agent.
    Type: Grant
    Filed: April 9, 2004
    Date of Patent: March 28, 2006
    Assignee: Firmenich SA
    Inventor: Alexandre Huboux
  • Publication number: 20040242693
    Abstract: A method of crystallizing optically active mandelic acids characterized in that it comprises adding alkali to an aqueous solution comprising optically active mandelic acids and mineral acid for partial neutralization, and then crystallizing the optically active mandelic acids from the aforementioned aqueous solution.
    Type: Application
    Filed: July 28, 2003
    Publication date: December 2, 2004
    Inventor: Norimasa Okuda
  • Publication number: 20040138445
    Abstract: The present invention includes a method for extracting bio-functional and bio-responsive fractions from biomass. The method includes providing biomass; treating the biomass with saturated steam at a time and temperature effective to extract bio-functional fractions; rapidly depressurizing the biomass and steam; mixing a depressurized bio-functional fraction with reagent that breaks down the fraction into oligomers and monomers; and separating the monomers from the each other and the oligomers using ion exchange.
    Type: Application
    Filed: September 24, 2003
    Publication date: July 15, 2004
    Inventor: Doug Van Thorre
  • Publication number: 20040138496
    Abstract: The present invention relates to a production method of (R)-3-hydroxy-3-(2-phenylethyl)hexanoic acid which comprises optical resolution of racemic 3-hydroxy-3-(2-phenylethyl)hexanoic acid with an optically active amine of the formula (VIII) 1
    Type: Application
    Filed: December 4, 2003
    Publication date: July 15, 2004
    Applicant: Sumika Fine Chemicals Co., Ltd.
    Inventors: Masahide Tanaka, Kozo Matsui, Tadashi Katsura, Mitsuhiro Iwasaki, Hiroshi Maeda, Nobushige Itaya
  • Publication number: 20040132998
    Abstract: Diketo- and pyridine-containing chiral crown ligands having at least two chiral bulky groups attached to two different chiral carbon atoms of the crown that are covalently bonded to or coated on suitable solid supports, and further coated by hydrophobic organic solvents are disclosed. These compositions and associated methods are characterized by selectivity of several target amine or amino acid enantiomers over their counter-enantiomers and derivatives. The composition preferably has an &agr;-value greater than or equal to 4. This allows for the separation of such enantiomers with non-chromatographic resin bed separations of three separation stages or less.
    Type: Application
    Filed: September 16, 2003
    Publication date: July 8, 2004
    Inventors: Ronald L. Bruening, Krzysztof E. Krakowiak
  • Publication number: 20040110957
    Abstract: In a process comprising synthesizing pyranes including [R—(R*,R*)]-N-[3-[1-[5,6-dihydro-4-hydroxy-2-oxo-6-(2-phenylethyl)-6-propyl-2H-pyran-3-yl]propyl]phenyl]-5-(trifluoromethyl)-2-pyridinesulfonamide the present invention comprises the improvements comprising: (a) providing a racemic mixture of 3-hydroxy-3-(2-phenylethyl)-hexanoate ethyl acetate by reacting said 1-phenyl-hexan-3-one with ethylbromoacetate under Reformatsky conditions; and (b) separating (R)-3-hydroxy-3-(2-phenylethyl)-hexanoic acid in enantiomeric excess by saponification and reverse resolution of the racemate of step (a) to produce a resolved product. In addition, the present invention comprises a reverse resolution process for separating an enantiomer from a mixture of enantiomers.
    Type: Application
    Filed: September 12, 2003
    Publication date: June 10, 2004
    Applicant: Honeywell International, Inc.
    Inventors: Joerg Wilken, Frank Nerenz, Andreas Kanschik-Conradsen
  • Publication number: 20040049049
    Abstract: A stereoselectively method of preparing a 1,2-disubstituted cycloalkyl, such as aminocycloalkyl ether compounds, from a trans-1,2-disubstituted cycloalkyl or a cis-2-substituted cycloalkanol. For example, a stereoselective method of preparing 1R-(3R-hydroxypyrrolidin-1-yl)-2R-(2-phenylethoxy)-cyclohexane from 1R,2R-cyclohexanediol or from meso-cis-1,2-cyclohexanediol is described. Aminocycloalkyl ethers, such as 1R-(3R-hydroxypyrrolidin-1-yl)-2R-(2-phenylethoxy)-cyclohexane, can be used to treat cardiac disease.
    Type: Application
    Filed: June 10, 2003
    Publication date: March 11, 2004
    Applicant: Johnson Matthey Pharmaceutical Materials, Inc.
    Inventors: Jurjus F. Jurayj, Emile Farhan, Pradeep K. Sharma
  • Publication number: 20040049071
    Abstract: A method of obtaining an enantioenriched organic compound comprising the steps of: 1) generating from a starting racemic, non-enantiopure or achiral compound a first mixture comprising at least one fluorous-tagged compound and at least one other non-fluorous tagged compound, at least one of these two compounds being enantioenriched relative to the starting compound; 2) contacting a first non-fluorous phase including the first mixture with a fluorous phase at a first phase interface, the fluorous-tagged compound distributing between the first non-fluorous phase and the fluorous phase; and 3) contacting the fluorous phase with a second non-fluorous phase at a second phase interface. The method further includes the step of having a third compound in the second non-fluorous phase that reacts with the fluorous-tagged compound to produce a second compound and the step of generating the first mixture by chemical or enzymatic kinetic resolution of a racemic or non-enantiopure compound.
    Type: Application
    Filed: May 21, 2003
    Publication date: March 11, 2004
    Inventors: Dennis Patrick Curran, Zhiyong Luo
  • Publication number: 20030105305
    Abstract: Methods for the separation of chaotropic and kosmotropic enantiomers within a racemic mixture are provided. Such methods comprise differentially partitioning the enantiomers into stabilized microdomains of low density water and high density water abutting a porous surface.
    Type: Application
    Filed: December 5, 2001
    Publication date: June 5, 2003
    Inventor: Phillipa M. Wiggins
  • Patent number: 6559338
    Abstract: A process for racemate resolution of 2-hydroxypropionic acids by reacting the racemic acid with an optically active base and subsequently separating off a diastereomeric salt of acid and base comprises using 1-(4-chlorophenyl)ethylamine as optically active base.
    Type: Grant
    Filed: April 25, 2001
    Date of Patent: May 6, 2003
    Assignee: BASF Aktiengesellschaft
    Inventors: Harald Bernard, Hartmut Riechers
  • Publication number: 20030045743
    Abstract: A method is provided for processing a solution having optical isomers to obtain a (2R,3S) target isomer: 1
    Type: Application
    Filed: June 27, 2001
    Publication date: March 6, 2003
    Inventors: James D. McChesney, Herbert R. Brinkman, Siead Zegar, David Baehr
  • Publication number: 20030004653
    Abstract: A method and workstation for optimizing separation of a given racemate automation technology, and computer-controlled design is disclosed. The workstation includes a synthesizer, an analyzer, a robot and computer in communication with the synthesizer and analyzer. The computer includes one or more programs for regulating variables such as types of stationary phases; types of solvents; amounts of solvents; pressure; temperature; and employs methods for optimizing separation of a given racemate and for designing optimized experiments for further investigation.
    Type: Application
    Filed: March 1, 2002
    Publication date: January 2, 2003
    Inventors: Michael Flavin, Sreenivasarao Vepachedu, David Zembower
  • Patent number: 6462229
    Abstract: (±)-&agr;-(Difluoromethyl)-ornithine is separate into its isomers using (−)-O,O′-di-p-toluoyl-L-tartaric acid. (−)-&agr;-(Difluoromethyl)-ornithine monohydrochloride monohydrate and in particular the (−)-isomer are inhibitors of ornithine decarboxylase and thereby have numerous pharmacological actions.
    Type: Grant
    Filed: July 20, 2001
    Date of Patent: October 8, 2002
    Assignee: Lonza Ltd.
    Inventor: Thomas Meul
  • Patent number: 6462221
    Abstract: The present invention relates to a method of preparing a 1-nitro-3-substituted-3-amino-2-propanol diastereomer represented by Structural Formula I: In Structural Formula I, R is an amine protecting group, and R1 is an amino acid side-chain, a protected amino acid side-chain, a substituted or unsubstituted aliphatic group, a substituted or unsubstituted aromatic group, a substituted or unsubstituted heteroaromatic group, a substituted or unsubstituted aralkyl or a substituted or unsubstituted heteroaralkyl group. The method involves contacting a 1-nitro-3-substituted-3-amino-2-propanone with a reducing agent to form a mixture of 1-nitro-3-substituted-3-amino-2-propanol diastereomers. The 1-nitro-3-substituted-3-amino-2-propanol diastereomers are then separated by simulated moving bed chromatography to obtain one or more 1-nitro-3-substituted-3-amino-2-propanol diastereomer.
    Type: Grant
    Filed: May 19, 2000
    Date of Patent: October 8, 2002
    Assignee: Pharm-Eco Laboratories, Inc.
    Inventors: Richard L. Gabriel, Adel M. Moussa, Sharon Fitzhenry, Changhua Liu, David A. Swanson, Brittany La, Salah Zahr, Yesh P. Sachdeva, Jurjus Jurayj
  • Patent number: 6458955
    Abstract: Improved processes for preparation of high enantiomeric purity compounds center on resolution using simulated moving bed chromatography of a racemic precursor early in the synthesis. Resolution is effected with high enantiomeric purity, and subsequent reactions of the desired enantiomer performed with high optical specificity to maintain enantiomeric purity. The undesired enantiomer is racemized and recycled to the resolution phase to avoid loss.
    Type: Grant
    Filed: November 3, 2000
    Date of Patent: October 1, 2002
    Assignee: UOP LLC
    Inventor: Mark J. Gattuso
  • Patent number: 6342629
    Abstract: There is provided a process for industrially and efficiently producing an optically active N-protected-N-methyl-4-halogenophenylalanine at a high purity, which is useful as an intermediate for the production of pharmaceutical agents. An optically active N-protected-N-methyl-4-halogenophenylalanine (including the free form and/or the salt form thereof) purified to a high purity is produced by way of the deposition and isolation in the form of salt (DCHA salt or the like) from an optically active N-protected-N-methyl-4-halogenophenylalanine containing at least the optical isomer thereof as an impurity. Because the intended compound at a high purity can be recovered and obtained at a high yield, the process of the present invention is very useful as a process for producing the intermediate for the production of pharmaceutical agents.
    Type: Grant
    Filed: February 1, 2000
    Date of Patent: January 29, 2002
    Assignee: Ajinomoto Co., Inc.
    Inventor: Masakazu Nakazawa
  • Patent number: 6207854
    Abstract: Disclosed a process for preparing substantially enantiomerically pure 3-amino-3-cyclopropylpropanoate esters, i.e., esters of 3-amino-3-cyclopropylpropanoic acid (3-cyclopropylalanine esters or 3-CPA esters) by a 5-step process wherein cyclopropanecarboxaldehyde (CPCA) is reacted with malonic acid and a source of ammonia to obtain 3-cyclopropylalanine (3-CPA); esterifying the 3-CPA; contacting the 3-CPA ester with a substantially enantiomerically pure acid selected from tartaric acid, dibenzoyltartaric acid and mandelic acid to obtain a diastereomeric salt of the 3-CPA ester and the acid; recrystallization of the salt to substantial diastereomeric purity; and neutralizing the salt to afford the substantially enantiomerically pure 3-CPA ester.
    Type: Grant
    Filed: December 15, 1999
    Date of Patent: March 27, 2001
    Assignee: Eastman Chemical Company
    Inventors: Daniel John Bayston, Virginie Falque, Ronald Michael Scott
  • Patent number: 6147254
    Abstract: A process for the preparation of carbocyclic stereoisomers of formulae (I), (I'), (IIA'), (IIB'), (VA') and (VB'), including enantiomerically pure (IIA'), (I) and (I') utilizing fractional crystallization of salts formed with a chiral base; a reducing agent; a protecting group removing agent or a protecting group providing agent.
    Type: Grant
    Filed: August 6, 1999
    Date of Patent: November 14, 2000
    Assignee: Glaxo Wellcome Inc.
    Inventors: Barry Riddle Sickles, Kenneth James Ingold, Christopher John Wallis
  • Patent number: 6093846
    Abstract: A process for preparing optically active 2-hydroxymethyl-3-phenylpropionic acid by resolving (RS)-2-hydroxymethyl-3-phenylpropionic acid via crystallization of an optically active amine salt, where the amine is optically active cis-1-amino-2-indanol salt, optically active .alpha.-methylbenzylamine salt, or optically active 3-methyl-2-phenyl-1-butylamine salt.
    Type: Grant
    Filed: November 30, 1999
    Date of Patent: July 25, 2000
    Assignee: Ajinomoto Co., Inc.
    Inventors: Hiroyuki Nohira, Takayuki Suzuki, Takayuki Hamada, Kunisuke Izawa
  • Patent number: 6090971
    Abstract: A process for the preparation of optically active phenylcyclohexylglycolate esters is described. The process utilizes carboxylic acid activation to couple (R)-- or (S)-cyclohexylphenylglycolic acid (CHPGA) with 4-N,N-diethylamino butynol or other propargyl alcohol derivatives. The preparation of the hydrochloride salt is also described. In addition, a resolution process employing tyrosine methyl ester enantiomers for preparing a single enantiomer of CHPGA from racemic CHPGA is disclosed.
    Type: Grant
    Filed: June 25, 1999
    Date of Patent: July 18, 2000
    Assignee: Sepracor Inc.
    Inventors: Roger P. Bakale, Jorge L. Lopez, Francis X. McConville, Charles P. Vandenbossche, Chris Hugh Senanayake
  • Patent number: 6087530
    Abstract: An object of the present invention is to provide a process for producing a .beta.-amino-.alpha.-hydroxy acid derivative via efficient and industrially utilizable steps.The present invention provides a process for producing a .beta.-amino-.alpha.-hydroxy acid derivative represented by the general formula (2) given below which comprises hydrolyzing an .alpha.-amino-.alpha.', .alpha.-dihaloketone derivative of the general formula (1) given below in the presence of a base, followed by protecting the amino group or without protecting the same.
    Type: Grant
    Filed: November 15, 1999
    Date of Patent: July 11, 2000
    Assignee: Kaneka Corporation
    Inventors: Shingo Matsumoto, Kazuhiko Matsuo, Tadashi Sugawa, Tadashi Moroshima, Kenji Inoue
  • Patent number: 6008403
    Abstract: A method for producing an optically active amino acid or derivative thereof having a high optical purity from an optically active amino acid comprising optical isomers or derivative thereof, which comprises any one of processes (A), (B), and (C), wherein the process (A) comprises the steps: (1) previously preparing an optically active amino acid or derivative thereof having an optical purity higher than a convergent value of a mutual solubility of the optical isomers and (2) crystallizing the optically active amino acid or the derivative thereof that exists in excess, said convergent value being a ratio of the desired optical isomer in the optical isomers dissolved in a mother liquor in which crystals of a racemate and an optically active compound coexist at equilibrium (the optical purity in a mother liquor). The processes (B) and (C) are described in the specification.
    Type: Grant
    Filed: September 26, 1997
    Date of Patent: December 28, 1999
    Assignee: Tosoh Corporation
    Inventors: Kimio Katsuura, Shigeaki Irino, Akira Tokuda
  • Patent number: 5994560
    Abstract: Described herein is a novel process to resolve a racemic compound into its optically active isomers without need for chemical transformation such as salt formation. The process advantageously utilizes polymers containing chiral moieties in their repeat units as well as exhibiting critical solution temperature behavior in a suitable solvent. An embodiment describes the resolution of tryptophan.
    Type: Grant
    Filed: August 29, 1996
    Date of Patent: November 30, 1999
    Assignee: Hoechst Celanese Corp.
    Inventors: Hyun Nam Yoon, Mengshi Lu, Naoya Ogata
  • Patent number: 5892112
    Abstract: Synthetic mammalian matrix metalloprotease inhibitors are disclosed that are useful for treating or preventing diseases wherein said diseases are caused by unwanted mammalian matrix metalloprotease activity and include skin disorders, keratoconus, restenosis, rheumatoid arthritis, wounds, cancer, angiogenesis and shock.
    Type: Grant
    Filed: January 21, 1994
    Date of Patent: April 6, 1999
    Assignees: Glycomed Incorporated, The University of Florida
    Inventors: Daniel E. Levy, Damian Grobelny, Cho Tang, Kevin R. Holme, Richard E. Galardy, Gregory S. Schultz, Asaad Nematalia, John H. Musser
  • Patent number: 5840964
    Abstract: A process for the preparation of 2-(2-fluoro-4-biphenyl)propianic acid enantiomers comprising a II order resolution of ketals of formula ##STR1## wherein R.sub.1 ad R.sub.2 have the meanings reported in the description; the asterisk shows the chiral carbon atom and the asymmetric carbon atoms marked by .alpha. and .beta. have both R or S configuration is described.
    Type: Grant
    Filed: December 22, 1995
    Date of Patent: November 24, 1998
    Assignee: Zambon Group S.P.A.
    Inventors: Claudio Pozzoli, Graziano Castaldi
  • Patent number: 5763647
    Abstract: A process for preparing an optically active 1,4-bridged-cyclohexane carboxylic acid derivatives which are clinically important thromboxane A.sub.2 thromboxane of formula (IV): ##STR1## wherein, R is phenyl or phenyl substituted with hydroxy, lower alkoxy, halogen, or lower alkyl; Y is oxygen, methylene, substituted methylene; m is 0 or 1; n is 0, 1 or 2; q is 3 or 4 with the proviso that when m is 1, n is 0 or 1 from an optically active norbornyl amine derivative.
    Type: Grant
    Filed: July 11, 1997
    Date of Patent: June 9, 1998
    Assignee: Shionogi & Co., LTD.
    Inventors: Mitsuaki Ohtani, Hisanori Takahashi, Fumihiko Watanabe, Masami Takayama
  • Patent number: 5739383
    Abstract: Described herein is a novel process to resolve a racemic compound into its optically active isomers without need for chemical transformation such as salt formation. The process advantageously utilizes polymers containing chiral moieties in their repeat units as well as exhibiting critical solution temperature behavior in a suitable solvent. An embodiment describes the resolution of tryptophan.
    Type: Grant
    Filed: November 26, 1996
    Date of Patent: April 14, 1998
    Assignee: Hoechst Celanese Corp.
    Inventors: Hyun-Nam Yoon, Mengshi Lu, Naoya Ogata
  • Patent number: 5721103
    Abstract: Novel trienoic compounds having activity for retinoic acid receptors and retinoid X receptors are provided. Also provided are pharmaceutical compositions incorporating such compounds and methods for their use.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: February 24, 1998
    Assignee: Ligand Pharmaceuticals Incorporated
    Inventors: Marcus F. Boehm, Lin Zhang, Youssef L. Bennani, Alex M. Nadzan
  • Patent number: 5510520
    Abstract: The present invention provides three optical resolution methods. The first aspect comprises the steps of adding an optically active bifunctional resolving reagent to a bifunctional compound to form a liquid material, precipitating crystals therefrom, and treating the crystals and the liquid material separately with an acidic material, a basic material, or a basic material and an acidic material, to obtain a pair of enantiomers of an optically active bifunctional compound. The second aspect comprises an optical resolution method by which one necessary enantiomer of a pair of enantiomers in an optically active bifunctional compound is exclusively obtained. The third aspect comprises a method for racemizing one unnecessary enantiomer of a pair of enantiomers in an optically active bifunctional compound which is formed by the optical resolution method of the present invention.
    Type: Grant
    Filed: August 19, 1994
    Date of Patent: April 23, 1996
    Assignee: Kankyo Kagaku Center Co., Ltd.
    Inventor: Masatoshi Kawashima