Resolution Per Se Of Optical Isomers Patents (Class 564/303)
  • Patent number: 8871978
    Abstract: A method for preparing a hop acid mixture having an enantiomeric excess of a (+)-tetrahydro-?-acid is disclosed. In the method, a racemate of a tetrahydro-?-acid is contacted with an amine to form a precipitate having an enantiomeric excess of the (+)-tetrahydro-?-acid. A method for preparing a hop acid is also disclosed. In the method, a racemate of a tetrahydro-?-acid is contacted with an amine to form a precipitate comprising a (+)-tetrahydro-?-acid, and the (+)-tetrahydro-?-acid is isomerized to a hop acid selected from the group consisting of (+)-trans-tetrahydro-iso-?-acids, (?)-cis-tetrahydro-iso-?-acids, and mixtures thereof, and reduced to (+)-trans-hexahydroiso-?-acids and (?)-cis-hexahydroiso-?-acids. An additive for flavoring a malt beverage is also disclosed. The additive includes a bittering agent selected from the group consisting of (+)-trans-tetrahydro-iso-?-acids, (?)-cis-tetrahydro-iso-?-acids, (+)-trans-hexahydroiso-?-acids, (?)-cis-hexahydroiso-?-acids, and mixtures thereof.
    Type: Grant
    Filed: May 20, 2011
    Date of Patent: October 28, 2014
    Assignee: MillerCoors LLC
    Inventors: Patrick L. Ting, Jason Pratt, David S. Ryder
  • Publication number: 20130018194
    Abstract: This invention relates to octahydro-binaphthol derivatives, which can recognize amino acids and amino alcohols enantioselectively and transform L-amino acids into D-amino acids and optically resolve amino acids or amino alcohol with high efficiency.
    Type: Application
    Filed: April 1, 2011
    Publication date: January 17, 2013
    Applicants: AMINOLUX, INC, EWHA UNIVERSITY-INDUSTRY COLLABORATION FOUNDATION
    Inventor: Kwan-Mook Kim
  • Patent number: 8350047
    Abstract: The present application relates to novel methods for the preparation of secondary carbinamine compounds, particularly the preparation of secondary carbinamine compounds of the formula Ia, formula Ib or formula IV from aldehydes of the formula II and boronic acids of the formula III or formula V, in the presence of ammonia or an ammonia equivalent of the formula NH4+X?.
    Type: Grant
    Filed: March 28, 2008
    Date of Patent: January 8, 2013
    Inventors: Avinash N. Thadani, Bhartesh Dhudshia
  • Patent number: 8067640
    Abstract: The present invention relates to a novel method for the preparation of diol intermediates having the formula (II) and/or the opposite enantiomer of an acylated diol having the formula (IV) useful for the preparation of escitalopram involving selective enzymatic acylation or deacylation.
    Type: Grant
    Filed: May 17, 2010
    Date of Patent: November 29, 2011
    Assignee: H. Lundbeck A/S
    Inventors: Naoki Taoka, Takahisa Kato, Shogo Yamamoto, Takashi Yoshida, Toshihiro Takeda, Yasuyoshi Ueda, Hans Petersen, Robert Dancer, Haleh Ahmadian, Lars O. Lyngso
  • Publication number: 20110288335
    Abstract: A method for preparing a hop acid mixture having an enantiomeric excess of a (+)-tetrahydro-?-acid is disclosed. In the method, a racemate of a tetrahydro-?-acid is contacted with an amine to form a precipitate having an enantiomeric excess of the (+)-tetrahydro-?-acid. A method for preparing a hop acid is also disclosed. In the method, a racemate of a tetrahydro-?-acid is contacted with an amine to form a precipitate comprising a (+)-tetrahydro-?-acid, and the (+)-tetrahydro-?-acid is isomerized to a hop acid selected from the group consisting of (+)-trans-tetrahydro-iso-?-acids, (?)-cis-tetrahydro-iso-?-acids, and mixtures thereof, and reduced to (+)-trans-hexahydroiso-?-acids and (?)-cis-hexahydroiso-?-acids. An additive for flavoring a malt beverage is also disclosed. The additive includes a bittering agent selected from the group consisting of (+)-trans-tetrahydro-iso-?-acids, (?)-cis-tetrahydro-iso-?-acids, (+)-trans-hexahydroiso-?-acids, (?)-cis-hexahydroiso-?-acids, and mixtures thereof.
    Type: Application
    Filed: May 20, 2011
    Publication date: November 24, 2011
    Inventors: Patrick L. Ting, Jason Pratt, David S. Ryder
  • Patent number: 7968748
    Abstract: A process for resolving a compound in racemic form comprising the following steps is described: a) reacting a compound in racemic form with a resolving agent, b) forming a diastereoisomeric complex of the resolving agent and an enantiomer of interest, c) separating the enantiomer of interest from the obtained diastereoisomer, wherein such a process is characterized in that said resolving agent is a compound of Formula (I). A diastereoisomeric complex between the resolving agent of Formula (I) and the enantiomer of interest is also described. The process according to the invention allows acid and basic racemic mixtures to be separated.
    Type: Grant
    Filed: February 1, 2007
    Date of Patent: June 28, 2011
    Assignee: Abiogen Pharma S.p.A.
    Inventors: Elio Napolitano, Rita Fiaschi, Chiara Bechini, Gabriella Brunetto
  • Publication number: 20100298572
    Abstract: The present application relates to novel methods for the preparation of secondary carbinamine compounds, particularly the preparation of secondary carbinamine compounds of the formula Ia, formula Ib or formula IV from aldehydes of the formula II and boronic acids of the formula III or formula V, in the presence of ammonia or an ammonia equivalent of the formula NH4+X?.
    Type: Application
    Filed: March 28, 2008
    Publication date: November 25, 2010
    Applicant: PANASONIC CORPORATION
    Inventors: Avinash N. Thadani, Bhartesh Dhudshia
  • Patent number: 7799952
    Abstract: The present invention relates to processes for preparing a compound of the general formula (Ia) wherein X is a halogen atom, or a pharmaceutically acceptable salt thereof, wherein a compound of the formula (II) wherein X is as defined above and Y and Z independently represent a leaving group each, is reacted with an optically active amino alcohol to form a first mixture of diastereomers.
    Type: Grant
    Filed: February 10, 2009
    Date of Patent: September 21, 2010
    Assignee: ratiopharm GmbH
    Inventors: Jiri Stohandl, Jaroslav Frantisek, Winfried Ness
  • Patent number: 7544840
    Abstract: The compound of formula (III), optionally its alkaline salt, is reacted with a compound of formula VII, wherein X is a leaving group, resulting in (S)-rivastigmine of formula II, which is then optionally converted into (S)-rivastigmine hydrogentartrade of formula I.
    Type: Grant
    Filed: October 21, 2003
    Date of Patent: June 9, 2009
    Assignee: Zentiva, a.s.
    Inventors: Hana Stepankova, Josef Hajicek, Stanislav Simek
  • Patent number: 7317127
    Abstract: The present invention provides a process for the optical resolution of racemic tomoxetine under reaction conditions that improve reaction yields and optical purity. The invention also provides an epimerization process for the (S)-(+) enantiomer. The invention further provides the conversion of the enantiomer obtained from the optical resolution into atomoxetine or a pharmaceutically acceptable salt thereof.
    Type: Grant
    Filed: June 28, 2005
    Date of Patent: January 8, 2008
    Assignee: Teva Pharmaceutical Fine Chemicals S.r.l
    Inventors: Eugenio Castelli, Giuseppe Lo Monaco, Silvia Mantovani, Paola Daverio, Paolo Riva, Alessandra Vailati, Stefano Bianchi
  • Patent number: 7256313
    Abstract: The invention relates to processes for preparing 3-aminomethyl-3,5,5-trimethylcyclo-hexylamine (isophoronediamine, IPDA) having a high cis/trans isomer ratio. IPDA having a cis/trans isomer ratio in the range from 63/37 to 66/34 can be obtained in any desired cis/trans isomer ratio, irrespective of temperature, by reacting IPDA with H2 and NH3 in the presence of a hydrogenation catalyst. IPDA having a cis/trans isomer ratio of at least 73/27 which is an important starting material for the synthesis of polyurethanes and polyamides can be obtained by combining this isomerization process with distillative processes.
    Type: Grant
    Filed: August 6, 2003
    Date of Patent: August 14, 2007
    Assignee: BASF Aktiengesellschaft
    Inventors: Frank Funke, Thomas Hill, Jobst RĂ¼diger Von Watzdorf, Wolfgang Mattmann, Wolfgang Harder, Erhard Henkes, Gerd Littmann, Manfred Julius
  • Patent number: 6878848
    Abstract: A process for interconverting a mixture of cis-trans isomers of a compound of formula I into the substantially pure cis isomer. Cis isomers of formula I are useful intermediates in the synthesis of cis isomers of benzamide piperidine compounds which exhibit activity as NK-1 receptor antagonists.
    Type: Grant
    Filed: November 10, 2003
    Date of Patent: April 12, 2005
    Assignee: Pfizer Inc
    Inventors: John Michael Humphrey, Norma Jacqueline Tom
  • Patent number: 6479702
    Abstract: The present invention relates to a compound which is expected to be a synthetic intermediate for medicines and pesticides or a separating agent for chromatography or a enantiomerically resolving agent for racemic bodies. That is, it provides 3-amino-1-indanol represented by the formula (I), a process for synthesizing it, an enantiomerically active compound of 3-amino-1-indanol and a process for enantiomerically resolving 3-amino-1-indanol, and a separating agent for enantiomeric isomers comprising enantiomerically active compound thereof as an effective ingredient. In the formula, the configuration between OH group and NH2 group are cis-configuration or trans-configuration and the compound may be a racemic body or an enantiomerically active compound.
    Type: Grant
    Filed: April 15, 2002
    Date of Patent: November 12, 2002
    Assignee: Daicel Chemical Industries, Ltd.
    Inventors: Kazuhiko Saigo, Kazushi Kinbara, Yoshiyuki Katsumata
  • 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: 6403832
    Abstract: There are disclosed are a diastereomer salt of formula (1): a process for producing the same, a process for producing optically active 3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid of formula (2′): a novel optically active amine compound of formula (4): a novel optically active amine compound of formula (8): an imine compound of formula (7) or (11):
    Type: Grant
    Filed: August 4, 2000
    Date of Patent: June 11, 2002
    Assignee: Sumitomo Chemical Company, Limited
    Inventors: Miyuki Oikawa, Hideki Ushio, Isao Kurimoto, Takayuki Higashii
  • Patent number: 6399829
    Abstract: (R*,R*)-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol (Tramadol) is synthesized in a Grignard reaction in the presence of an additive resulting in a higher trans:cis ratio of product than is obtained in the absence of the additive. The Grignard reaction between 3 bromoanisole and the appropriate Mannich base in the presence of an amine or ether additive gives the amine product in an improved trans/cis ratio. The base is converted to its hydrochloride and recrystallized from a low molecular weight nitrile such as acetonitrile until a greater than 98% trans/cis ratio is obtained. Recrystallization from isopropanol gives (R*,R*)2-[(dimethylamino)methyl]-1-(3-metboxyphenyl)cyclohexanol hydrochloride free of the nitrile solvent. A hydrochloride of Tramadol can be synthesized without increasing a ratio of trans:cis by including a step in which HCl is added to Tramadol base in the presence of toluene.
    Type: Grant
    Filed: November 20, 2000
    Date of Patent: June 4, 2002
    Assignee: Mallinckrodt Inc.
    Inventors: Esa T. Jarvi, Neile A. Grayson, Robert E. Halvachs
  • Patent number: 6365756
    Abstract: A process for the production of optically enriched (R)- or (S)-albuterol or (R)- or (S)-albuterol salts by the resolution of a novel ketal derivative 2-(N-t-butylamino)-1-(+2,2-dimethyl-1,2-benzodioxin-6-yl) ethanol, with a chiral tartaric acid derivative.
    Type: Grant
    Filed: November 13, 2000
    Date of Patent: April 2, 2002
    Assignee: Fine Chemical Corporation Limited
    Inventors: Anne Stevens, Roger Hunter, Luigi Nassimbeni, Mino Caira, Janet Scott, Rainer Clauss, Joanne Gibson, Tarron Grimmbacher
  • Publication number: 20020019491
    Abstract: Naphthyl crown ether ligand molecules containing at least two naphthyl groups that are covalently bonded to suitable solid supports and coated by hydrophobic organic solvents are disclosed. These compositions and associated methods are characterized by selectivity of desired 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 nonchromatographic resin bed separations of three separation stages or less.
    Type: Application
    Filed: March 8, 2001
    Publication date: February 14, 2002
    Applicant: IBC Advanced Technologies, Inc.
    Inventors: Ronald L. Bruening, Krzysztof E. Krakowiak
  • Patent number: 6316671
    Abstract: This invention relates to a method of splitting 1-amino-alkan-2-ol compounds of general formula: in which the group R can represent a wide variety of linear, branched or cyclic alkyl groups, comprising up to about 20 to 25 carbon atoms and preferably 1 to 15 carbon atoms. These groups can possibly have one or more double bonds, one or more hetero-atoms such as oxygen or sulfur so long as these are to be found separated from the asymmetric carbon atom by at least one carbon link and do not destroy the aliphatic nature of the group R. These groups can also be substituted by one or more halogen atoms such as chlorine or lower alkoxy groups such as methoxy or ethoxy groups.
    Type: Grant
    Filed: May 28, 1999
    Date of Patent: November 13, 2001
    Assignee: Universite de Rouen
    Inventors: Gerard Coquerel, Lionel Catroux, Yvette Combret
  • Patent number: 6265614
    Abstract: Intermediates having the formula wherein BI is —CH2OH or —CH2ORP, and RP is an alcohol protecting group; a is 1, 2, or 3; TI is —OH or QI is phenyl, naphthyl ohr heteroaryl having 1-3 substituents; Ra and Rc are the same, and are H, or are selected from alkyl, cycloalkyl and aryl groups, the groups being optionally substituted with one or more substituents selected from alkyl cycloalkyl, aryl, or —OH; or Ra and Rc together with the C—N—C chain to which they are bound, form a 5-7 membered ring; Rb and Rd are the same, and are H, or are selected from alkyl, cycloalkyl and aryl groups, the groups being optionally substituted with one or more substituents selected from alkyl, cycloalkyl, aryl, or —OH; and D is a directing group capable of directing lithiation alpha to a nitrogen atom of a nitrogen compound having D as a substituent bound to the nitrogen atom when the nitrogen compound is reacted with s-butyl lithium, are disclosed
    Type: Grant
    Filed: October 13, 2000
    Date of Patent: July 24, 2001
    Assignee: Schering Corporation
    Inventors: Anantha R. Sudhakar, Suhan Tang
  • Patent number: 6235927
    Abstract: A diastereomer complex obtained via a process for the separation of enantiomers is disclosed, wherein separation can be rapidly effected such that enantiomers are obtained with high e.e. values. The process pets the separation of mixtures of enantiomers in which more than one resolving agent is used, of which at least one resolving agent is optically active, and which yields a diastereomer complex containing at least two resolving agents in optically active form. The process provides for, inter alia, a diastereomer complex having at least three compounds of which at least two compounds are resolving agents in optically active form, and at least one compound is an onantiomer in optically active form. Also provided is a diastereomer complex having at least three compounds of which at lea one compound is a resolving agent in optically active form, and at least two compounds which are enantiomers in optically active form.
    Type: Grant
    Filed: October 22, 1997
    Date of Patent: May 22, 2001
    Assignee: DSM N.V.
    Inventors: Ton R. Vries, Hans Wijnberg, Erik Van Echten, Lumbertus A. Hulshof, Quirinus B. Broxterman
  • Patent number: 6184381
    Abstract: This document describes a novel and practically excellent process for the preparation of optically active compounds, such as optically active alcohols or amines which are useful for various applications, for example, as synthetic intermediates of pharmaceuticals, liquid crystal materials, and reagents for optical resolution, wherein a hydrogen transfer type asymmetric reduction is carried out in the presence of both a transition metal complex and an optically active nitrogen compound or a transition metal complex having an optically active nitrogen compounds as an asymmetric ligand, and a hydrogen-donating organic or inorganic compound.
    Type: Grant
    Filed: September 29, 1998
    Date of Patent: February 6, 2001
    Assignees: Japan Science & Technology Corp., NKK Corp., Takeda Chemical Industries, Asahi Kasei Kogyo Kabushiki Kaisha, Takasago Intl. Corp.
    Inventors: Takao Ikariya, Shohei Hashiguchi, Jun Takehara, Nobuyuki Uematsu, Kazuhiko Matsumura, Ryoji Noyori, Akio Fujii
  • Patent number: 5986135
    Abstract: An improved process for the preparation of (S)-1,1,1-trifluoroalkyl-2-amines of formula IIIA, ##STR1## where R.sup.1 is a C.sub.1-6 alkyl group, from the corresponding racemic mixture, which process includes treating 1 part by mole of the racemic mixture with approximately 0.3 to 0.7 part by mole of D-(-)-tartaric acid in the presence of an inert solvent.
    Type: Grant
    Filed: September 25, 1998
    Date of Patent: November 16, 1999
    Assignee: American Cyanamid Company
    Inventors: Waldemar Pfrengle, Klaus-Juergen Pees, Guido Albert, Paul Carter, Annerose Rehnig, Henry Van Tuyl Cotter
  • Patent number: 5977409
    Abstract: This invention relates to the use of a family of chiral .alpha.-substituted benzylamine reagents during chemical synthesis. Specifically, the reagents can be used in an auxiliary manner to deliver either a substituted or unsubstituted nitrogen atom while simultaneously bestowing an asymmetric bias toward the formation and separation of the diastereomeric intermediates that result from reaction of the reagents with racemic substrates also having one or more asymmetric atoms. The chiral auxiliary portion of the reagents can then be readily removed at some later and convenient stage of the overall synthetic scheme. The initial nitrogen-delivery reaction, asymmetric separation procedures, and removal of the chiral auxiliary can all be conducted under routine experimental conditions, including the final debenzylation, such that the overall method is adaptable to large-scale chemistry.
    Type: Grant
    Filed: April 14, 1998
    Date of Patent: November 2, 1999
    Assignee: University of Toledo
    Inventor: Paul W. Erhardt
  • Patent number: 5885787
    Abstract: In accordance with a novel process, (R)-amines of the formula ##STR1## in which R.sup.1, R.sup.2 and n have the meanings given in the description, can be prepared by reacting reating N-acyl-amines of the formula ##STR2## in which R.sup.1, R.sup.2, R.sup.3 and n have the meanings given in the description,with lipases which are suitable for cleaving the (R)-enantiomers of N-acyl-amines of the formula (II), in the presence of water and optionally in the presence of an organic diluent, at a pH of between 3.0 and 10.0 and at temperatures of between 0.degree. C. and 80.degree. C.
    Type: Grant
    Filed: August 25, 1997
    Date of Patent: March 23, 1999
    Assignee: Bayer Aktiegesellschaft
    Inventors: Hauke Smidt, Andreas Fischer, Peter Fischer, Rolf D. Schmid, Uwe Stelzer
  • 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: 5723667
    Abstract: A method of producing optically active tert-leucinol (formula I) of high enantiomeric purity ##STR1## by converting racemic (RS)-tert-leucinol into a diastereomeric salt pair by reaction with an optically active acid, removing the salt pair from solution by fractionated crystallization and separating therefrom the optically active acid to release the optically active tert-leucinol from the salt. The optically active acid used is an N-acylated tert-leucine of general formula VIII: ##STR2## in which R can be hydrogen or an alkyl-, arylalkyl- or aryl group with up to 20 C atoms and * signifies a chirality center.
    Type: Grant
    Filed: February 21, 1996
    Date of Patent: March 3, 1998
    Assignee: Degussa Aktiengesellschaft
    Inventors: Karlheinz Drauz, Wilfried Jahn, Michael Schwarm
  • Patent number: 5639913
    Abstract: Novel derivatives of 1-aminoindan and their salts are described. Optically active 1-aminoindan derivatives are prepared by reacting a N-benzyl analog of the desired compound with an enantiomer of mandelic acid.
    Type: Grant
    Filed: September 13, 1996
    Date of Patent: June 17, 1997
    Assignee: Teva Pharmaceutical Industries, Ltd.
    Inventors: Ramy Lidor, Eliezer Bahar
  • Patent number: 5541080
    Abstract: A process is provided for preparing an L-.alpha.-amino acid from a 5(4H)-oxazolone precursor. The precursor is subjected to a two-step process sequence in which the precursor is first contacted with a methanolytically active lipase in the presence of methanol in a non-polar solvent to enantioselectively solvolyze the precursor and produce an intermediate optically active methyl ester of the desired .alpha.-amino acid. This ester is then contacted with a protease in the presence of water to enantioselectively cleave the ester and accomplish an enzymatic kinetic resolution to prepare the product L-.alpha.-amino acid in high optical purity.
    Type: Grant
    Filed: May 28, 1993
    Date of Patent: July 30, 1996
    Assignee: Wisconsin Alumni Research Fdn.
    Inventor: Charles J. Sih
  • Patent number: 5442117
    Abstract: A process for obtaining a substantially pure enantiomer of an hydrocarbyl amine is described. The process utilizes first an enantiomerically enriched mixture the of hydrocarbyl amine obtained from kinetic resolution, diastereomeric crystallization or asymmetric synthesis processes. This enriched mixture is reacted with an inorganic acid producing a salt that has the following properties:1) has at least one eutectic point;2) a composition that is not at the eutectic point; and3) a eutectic composition that is closer to the racemiccomposition than is the eutectic composition of saidhydrocarbyl, or be a solid where the salt is a liquid. A substantially pure, enantiomeric salt is separated, leaving a mother liquor comprising the solvent and the hydrocarbyl amine enriched in the other enantiomer.
    Type: Grant
    Filed: December 13, 1993
    Date of Patent: August 15, 1995
    Assignee: Albemarle Corporation
    Inventors: G. Patrick Stahly, Thanikavelu Manimaran
  • Patent number: 5435919
    Abstract: Optically-active, amphiphilic, free-radical addition copolymers having an optically-active hydrophobic portion and an ionic hydrophilic portion are effective resolving agents. This utility is based on a unique combination of properties, viz., water solubility, chirality and amphiphilicity, i.e., having a dual hydrophobic and hydrophilic nature.
    Type: Grant
    Filed: November 17, 1994
    Date of Patent: July 25, 1995
    Assignee: The Dow Chemical Company
    Inventors: Mladen Ladika, Thomas E. Fisk
  • Patent number: 5391634
    Abstract: Optically-active, amphiphilic, free-radical addition copolymers having an optically-active hydrophobic portion and an ionic hydrophilic portion are effective resolving agents. This utility is based on a unique combination of properties, viz., water solubility, chirality and amphiphilicity, i.e., having a dual hydrophobic and hydrophilic nature.
    Type: Grant
    Filed: January 21, 1994
    Date of Patent: February 21, 1995
    Assignee: The Dow Chemical Company
    Inventors: Mladen Ladika, Thomas E. Fisk
  • Patent number: 5367091
    Abstract: This invention refers to a new process for the preparation of D-(-)-3-acetylthio-2-methylpropionic acid, an important intermediate in the synthesis of the antihypertensive Captopril, consisting of the resolution of the racemic mixture of said acid through formation of the mixture of the diastereomeric salts thereof, in an appropriate solvent, with the low molecular weight L-(+)-2-aminobutanol as a base, selective crystallization of the diastereomeric salt of D-(-)-3-acetylthio-2-methylpropionic acid with L-(+)-2-aminobutanol and release of the D-(-)-3-acetylthio-2-methylpropionic acid through displacement of the base with a stronger acid.
    Type: Grant
    Filed: October 19, 1993
    Date of Patent: November 22, 1994
    Assignee: Medichem, S.A.
    Inventors: Alberto Stampa Diez Del Corral, Maria del Carmen Onrubia Miguel, Jose Irurre Perez
  • Patent number: 5306826
    Abstract: The present invention relates to a process for the preparation of optically active amino acid amide. L-amino and D-amino acid amides are mixed in the presence of 0.5-4 equivalents of an aldehyde, relative to the quantity of amino acid amide, in the presence of a solvent and water. The mixture is converted in whole or in part by means of an optically active carboxylic acid into a salt of the amino acid amide and the carboxylic acid. A portion mainly consisting of one of the diastereoisomers of that salt is separated from the reaction mixture obtained. Instead of a mixture of L-amino and D-amino acid amides, it is also possible to use a mixture of the Schiff bases of an amino acid amide and an aldehyde, in which case it is not necessary to add extra aldehyde, and the required quantity of water amounts to at least 1 equivalent relative to the quantity of Schiff base. With this process, a high yield of optically active amino acid amide or the corresponding amino acid is rapidly obtained.
    Type: Grant
    Filed: February 15, 1991
    Date of Patent: April 26, 1994
    Assignee: Stamicarbon B.V.
    Inventor: Wilhelmus H. J. Boesten
  • Patent number: 5292893
    Abstract: A process is provided for catalytically reducing imines, oximes, hydrazones and related compounds. Moreover, there is provided a process for the catalytic asymmetric reduction of imines, oximes, hydrazones, and the like, using enantiomerically enriched catalysts, to provide chiral amine reaction products which are enriched in one enantiomer. Catalytic asymmetric reduction can also be carried out using an achiral precatalyst in combination with aThe U.S. Government has rights in this invention pursuant to NIH Grant Number GM 34917.
    Type: Grant
    Filed: November 14, 1991
    Date of Patent: March 8, 1994
    Assignee: Massachusetts Institute of Technology
    Inventors: Stephen L. Buchwald, Christopher A. Willoughby
  • Patent number: 5281750
    Abstract: The present invention relates to chiral supports and to their use in the asymmetric synthesis, deracemization and optical inversion of organic chiral compounds. In particular, the supports are used in combination with thermal equilibration of a species having a reactive achiral portion. Preferably, these supports are obtained by the copolymerization of at least one chiral unit and at least one functionalizing unit or by the polymerization of at least one chiral unit which is a source of said functionalizing unit. Optionally, a crosslinking agent is utilized. By utilizing these supports and thermal equilibration, excess enantiomers can be produced.
    Type: Grant
    Filed: November 16, 1992
    Date of Patent: January 25, 1994
    Assignee: Rhone-Poulenc Chimie
    Inventors: Robert Jacquier, Monique Calmes, Jacques Daunis
  • Patent number: 5280093
    Abstract: The present invention relates to chiral polymers and to their uses for operations of asymmetric synthesis, deracemization and optical inversion.These polymers are characterized in that they comprise:a chiral unita functionalizing unitan optional crosslinking unitApplication to chiral organic synthesis.
    Type: Grant
    Filed: April 14, 1993
    Date of Patent: January 18, 1994
    Assignee: Rhone-Poulenc Chimie
    Inventors: Robert Jacquier, Monique Calmes, Jacques Daunis
  • Patent number: 5274118
    Abstract: A process for the preparation of (2R)-methyl-4,4,4-trifluorobutylamine, or an acid addition salt thereof which comprisesa) acylating an optically active amine with 2-methyl-4,4,4-trifluorobutanoic acid or a reactive derivative thereof to afford a butyramide;b) separating (R)-diastereomeric butyramide from (S)-diastereomeric butyramide; andc) converting the (R)-diastereomeric butyramide into the desired (2R)-methyl-4,4,4-trifluorobutylamine, or an acid addition salt thereof. The product may be acylated with a carboxylic acid of formula III ##STR1## wherein U is carboxy, or a reactive derivative thereof to afford (R)-4-[5-(N-[4,4,4-trifluoro-2-methylbutyl]carbamoyl)-1-methylindol-3-yl-m ethyl]-3-methoxy-N-o-tolylsulphonylbenzamide. The indole is useful as a leukotriene antagonist, for example in the treatment of asthma or allergic rhinitis.
    Type: Grant
    Filed: December 4, 1991
    Date of Patent: December 28, 1993
    Assignee: Imperial Chemical Industries PLC
    Inventors: Robert T. Jacobs, Andrew G. Brewster, George J. Sependa
  • Patent number: 5225591
    Abstract: The disclosed process relates to a method for preparing 1-cyclopentylalkyl amines, useful in the synthesis of artificial sweeteners, by reducing an azanorbornene in a high-yield one-step reduction of an azanorbornene, wherein the method involves use of a solvent reductant system with catalyst that is compatible with the production of edible food compositions.
    Type: Grant
    Filed: July 28, 1992
    Date of Patent: July 6, 1993
    Assignee: The Coca-Cola Company
    Inventors: James G. Sweeny, Lihong L. D'Angelo
  • Patent number: 5200561
    Abstract: Disclosed is a process for producing an optically active amine represented by the formula (IV) ##STR1## wherein R.sub.7 and R.sub.8 each denote an alkyl group, aryl group or aralkyl group, providing that they do not denote the same group at the same time, and * indicates an asymmetric carbon atom, which comprises reacting an asymmetric reducing agent obtained from (1) an optically active amine derivative represented by the formula (I) ##STR2## wherein R.sub.1 denotes an alkyl group, aryl group or aralkyl group; R.sub.2 denotes a hydrogen atom, alkyl group or aralkyl group; R.sub.3 denotes an aryl group or a substituent represented by the formula (II) ##STR3## wherein R.sub.4 and R.sub.5 each denote a hydrogen atom, aryl group or aralkyl group, and * is as defined above, (2) a metal borohydride and (3) sulfuric acid, with either the syn-isomer or the anti-isomer of an oxime derivative represented by the formula (III) or with a mixture rich in either one of the two isomers ##STR4## wherein R.sub.
    Type: Grant
    Filed: October 7, 1991
    Date of Patent: April 6, 1993
    Assignee: Sumitomo Chemical Company, Limited
    Inventors: Naoto Konya, Yukio Yoneyoshi, Yoji Sakito, Shinji Nishii, Gohfu Suzukamo, Hiroko Sakane
  • Patent number: 5166397
    Abstract: This invention relates to a process for producing an optically active cyclobutylamine which comprises reacting a racemic modification of cyclobuthylamine represented by the following general formula [I]: ##STR1## wherein R.sup.1 and R.sup.2 represent each a hydrogen atom or a protecting group; with an optically active N-acylphenylglycine to thereby give two corresponding diastereomeric salts, crystallizing the more difficultly soluble diastereomeric salt and isolating the corresponding optically active cyclobutylamine from the diastereomeric salt thus crystallized. The optically active substances of the compound of the above general formula [I] are useful as, for example, an intermediate in the synthesis of 9-[(1R, 2R, 3S)-2,3-bis(hydroxymethyl)-1-cyclobutyl]guanine which is expected as an antiviral agent.
    Type: Grant
    Filed: September 10, 1991
    Date of Patent: November 24, 1992
    Assignee: Nippon Kayaku Kabushiki Kaisha
    Inventors: Kazuhisa Narita, Masashi Nagai, Hideo Sugimura, Yukihiro Sagawa, Akira Shiozawa
  • Patent number: 5145998
    Abstract: A method for producing an optically active amine which is an important compound as a resolving agent for medicines, agricultural chemicals, intermediates thereof, etc is disclosed.
    Type: Grant
    Filed: October 2, 1990
    Date of Patent: September 8, 1992
    Assignee: Sumitomo Chemical Company, Limited
    Inventors: Yoji Sakito, Gohfu Suzukamo, Yukio Yoneyoshi
  • Patent number: 5120853
    Abstract: The optically active benzylamine derivatives of the present invention are very useful for use as the asymmetric ligand of an asymmetric reducing agent. By using the optically active amine-boron complex prepared from the compound of the present invention, optically active products can be obtained in a specifically high optical yield. Moreover, the separation and recovery of the reaction products and asymmetric ligand can be easily achieved.
    Type: Grant
    Filed: February 8, 1991
    Date of Patent: June 9, 1992
    Assignee: Sumitomo Chemical Company, Limited
    Inventors: Yukio Yoneyoshi, Gohfu Suzukamo, Yoji Sakito
  • Patent number: 5110987
    Abstract: A method of preparing a substituted derivative of sphingosine comprising the steps of reducing serine methyl ester by a hydride reagent to form an aldehyde or aldehyde derivative, adding acetylide anions to the aldehyde to form an erythro-isomer or propargyl alcohol and inverting the propargyl alcohol by S.sub.N 2 inversion to form a threo-isomer. Either isomer can then be deprotected to form an alkyne with a 2-aminopropane 1,3-diol head group; this alkyne can be reduced to form sphingosine or a sphingosine derivitive which can be functionalized at the 4 and 5 positions to form a substituted derivative of sphingosine.
    Type: Grant
    Filed: June 17, 1988
    Date of Patent: May 5, 1992
    Assignee: Emory University
    Inventors: Dennis Liotta, Alfred H. Merrill
  • Patent number: 5087700
    Abstract: A novel process for producing hindered and unhindered primary amines represented by the formula RNH.sub.2 and R*NH.sub.2 in high yields from novel intermediates RBMe.sub.2 or R*BMe.sub.2 wherein R is an organo group, R* is a chiral organo group, attached to boron, B is boron and Me is methyl.
    Type: Grant
    Filed: March 26, 1990
    Date of Patent: February 11, 1992
    Assignee: Aldrich Chemical Company, Inc.
    Inventor: Herbert C. Brown
  • Patent number: 5087753
    Abstract: Process for recovering .alpha.-aminoalcohols by extraction from aqueous solutions, in which process an aromatic aldehyde is added at elevated pH to an aqueous solution of an aminoalcohol in an at least equimolar amount in respect of the aminoalcohol, the resulting mixture is converted with formation of the Schiff base of the aldehyde and the aminoalcohol and the aqueous solution is subsequently extracted using a water-immiscible organic solvent, upon which the Schiff base in the resulting extract is hydrolized and the .alpha.-aminoalcohol or a salt thereof is recovered.
    Type: Grant
    Filed: September 19, 1990
    Date of Patent: February 11, 1992
    Assignee: Stamicarbon B.V.
    Inventors: Wilhelmus H. J. Boesten, Catharina H. M. Schepers, Mathieu J. A. Roberts
  • Patent number: 5041655
    Abstract: An improved method of preparing 1,6-di(N.sup.3 -cyano-N.sup.1 -guanidino) hexane from alkali dicyanamide and a hexamethylene diammonium salt in alcoholic solution or suspension. The reaction is carried out in the presence of a limited amount of water and of a catalytic amount of a base, preferably a tertiary amine. The pH of the reaction mixture at the start of the reaction is 8 to 10. After the reaction is over, the reaction mixture is compounded with water at a temperature above 80.degree. C. and the coarse product which crystallizes out is separated from the liquid phase.Preferably, sodium dicyanamide and hexamethylene diamine dihydrochloride, preferably formed in situ from aqueous 1,6-diaminohexane and aqueous hydrochloric acid, are reacted at pH 9-9.5 in n-butanol in the presence of 0.1 to 20% by wt. water in relation to the solvent including water.1,6-di(N.sup.3 -cyano-N.sup.
    Type: Grant
    Filed: September 6, 1988
    Date of Patent: August 20, 1991
    Assignee: Degussa Aktiengesellschaft
    Inventors: Klaus Huthmacher, Axel Kleemann, Horst Bethge, Rolf Braun
  • Patent number: 5039801
    Abstract: The invention provides an improved method for obtaining optically active amines, carbamates, and isocyanates by thermal fragmentation of optically active ureas through refluxing the ureas in C.sub.3 -C.sub.7 alcohol solution with or without catalytic amounts of alkali metal.
    Type: Grant
    Filed: August 28, 1987
    Date of Patent: August 13, 1991
    Assignee: The United States of America as represented by the Department of Health & Human Services
    Inventors: Arnold Brossi, Bernhard Schonenberger
  • Patent number: 5011995
    Abstract: Asymmetric hydrogenation of prochiral N-aliphatic ketimines to give optically active secondary amines at a temperature from -20.degree. to 80.degree. C., a hydrogen pressure of 10.sup.5 to 10.sup.7 Pa, with the addition of catalytic amounts of an iridium compound of the formula III or IIIa[XIrYZ] (III)or[XIrY].sup..sym. A.sup..crclbar. (IIIa)in which X is two olefin ligands or a diene ligand, Y is a chiral diphosphine the secondary phosphine group of which are attached through 2-4 C atoms and which, together with the Ir atom, forms a 5-membered, 6-membered or 7-membered ring, or Y is a chiral diphosphinite the phosphinite groups of which are attached via 2 C atoms and which, together with the Ir atom, forms a 7-membered ring, Z is Cl, Br or I and A.sup.- is the anion of an oxygen acid or complex acid, and, if appropriate, with the addition of an ammonium chloride, bromide or iodide or an alkali metal chloride, bromide or iodide.
    Type: Grant
    Filed: July 19, 1988
    Date of Patent: April 30, 1991
    Assignee: Ciba-Geigy Corporation
    Inventors: Benoit Pugin, Gerardo Ramos, Felix Spindler
  • Patent number: 4990666
    Abstract: A process for racemization of optically active amino alcohols by subjecting the amino alcohol to hydrogen under moderate temperature and pressure conditions while in contact with Raney cobalt.
    Type: Grant
    Filed: February 4, 1987
    Date of Patent: February 5, 1991
    Assignee: W. R. Grace & Co.-Conn.
    Inventor: Stephen G. Harsy