By Salt Formation Patents (Class 564/425)
-
Patent number: 8063251Abstract: A process for the preparation of optically pure R (?) salbutamol of formula (6) and its pharmaceutically acceptable salts by using a (+) 4-nitro tartranilic acid as the resolving agent and a binary solvent system comprising alkyl acetate and C1 to C4 branched or normal chain alcohol for dissolution of the racemic mixture and resolving agent and purification of the 4-nitro tartranilic acid salt of R (?) salbutamol. 4-nitro tartranilic acid salt of R (?) salbutamol is converted into formic acid salt of R (?) 4-benzyl salbutamol followed by basification and debenzylation to form optically pure R (?) salbutamol. Optically pure (R)-salbutamol is obtained in good yield and high purity. The optically pure R (?) salbutamol is optionally converted into pharmaceutically acceptable salts.Type: GrantFiled: September 25, 2006Date of Patent: November 22, 2011Assignee: Aarti Healthcare LimitedInventors: Parimal Hasmukh Desai, Narendra Jagannath Salvi, Bharatkumar Surendra Patravale, Subramanian Seetharaman, Dilip Jibhau Patil, Khandu Shankar Ghogare
-
Patent number: 7884247Abstract: Novel 3-[2-(dimethylamino)methyl-(cyclohex-1-yl)]-phenol maleate compounds corresponding to formula I and processes for preparing these compounds are provided. Pharmaceutical compositions including these compounds and methods of treating or alleviating pain with these compounds are also provided.Type: GrantFiled: July 24, 2006Date of Patent: February 8, 2011Assignee: Gruenenthal GmbHInventors: Michael Gruss, Wolfgang Hell, Martin Szelagiewicz, Joerg Berghausen, Susan Margaret De Paul, Markus Von Raumer
-
Publication number: 20090069582Abstract: This patent discloses a method for resolution of 4-[4-(dimethylamino)-1-(4?-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)-benzonitrile as a racemic or non-racemic enantiomer mixture into its isolated enantiomers, said method comprising the step of fractionally crystallizing 4-[4-(dimethylamino)-1-(4?-fluoro-phenyl)-1-hydroxybutyl]-3-(hydroxymethyl)-benzonitrile as a salt with the (+)—(S,S)— or (?)—(R,R)-enantiomer of O,O?-di-p-toluoyl-tartaric acid in a solvent system comprising 1-propanol, ethanol or acetonitrile.Type: ApplicationFiled: September 2, 2008Publication date: March 12, 2009Applicant: H. Lundbeck A/SInventors: Carla De Faveri, Florian Anton Martin Huber, Robert Dancer
-
Patent number: 7317127Abstract: 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: GrantFiled: June 28, 2005Date of Patent: January 8, 2008Assignee: Teva Pharmaceutical Fine Chemicals S.r.lInventors: Eugenio Castelli, Giuseppe Lo Monaco, Silvia Mantovani, Paola Daverio, Paolo Riva, Alessandra Vailati, Stefano Bianchi
-
Patent number: 7262327Abstract: Provided is a recycling process for preparing sertraline, which may be carried out on an industrial scale.Type: GrantFiled: September 7, 2004Date of Patent: August 28, 2007Assignee: Teva Pharmaceutical Industries Ltd.Inventors: Marioara Mendelovici, Ben-Zion Dolitzky, Marina Yu Etinger, Gennady A. Nisnevich
-
Patent number: 7122700Abstract: A method for bisformylation an arylamine compound by reacting an arylamine compound with an alkyleneamine in a reaction mixture while refluxing an acid in the reaction mixture.Type: GrantFiled: July 30, 2004Date of Patent: October 17, 2006Assignee: Xerox CorporationInventors: Timothy P. Bender, Nan-Xing Hu, H. Bruce Goodbrand
-
Patent number: 6965832Abstract: Apparatus and a method are described for investigating polymorphs of a material, isomers of a material which allow different isomeric forms to be resolved, different hydrates/solvates and/or different salts of a material. The apparatus comprises an assembly (2) of reactor devices (6) arranged within a reactor body (8) which incorporates a heating/cooling block (10) and a stirrer block (12). A vessel support block (14) supports respective sample vessels (15) below each reactor device (6) for recieving material from the reactor devices. The apparatus includes a control unit (4) which includes a computer (16) which controls a robot for delivering materials to the reactor devices; a heating/cooling unit (18); a stirrer control unit (20); and a pressure unit (22) which controls the passage of material from the reactor devices (6) to the sample vessels (15).Type: GrantFiled: April 9, 2001Date of Patent: November 15, 2005Assignee: Millennium Pharmaceuticals, Inc.Inventors: Ryszard Kobylecki, Daniel Cowell, Vassllis Stylianopoulos
-
Patent number: 6909017Abstract: The invention relates to a method for isolating and purifying (1RS,2RS)-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)-cyclohexanol as a saccharinate from a mixture of the diastereomers (1SR,2)RS-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)-cyclohexanol and (1SR-2RS)-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)-cyclohexanol and optionally impurities.Type: GrantFiled: August 11, 2003Date of Patent: June 21, 2005Assignee: Grunenthal GmbHInventor: Wolfgang Hell
-
Patent number: 6906087Abstract: Crystalline forms of Venlafaxine hydrochloride were found, referred to hereinafter as polymorphic Forms A, B and D. Furthermore, the present invention is directed to processes for the preparation of these crystalline forms and pharmaceutical compositions comprising the crystalline forms.Type: GrantFiled: October 23, 2001Date of Patent: June 14, 2005Assignee: Ciba Specialty Chemicals CorpationInventors: Paul Adriaan Van Der Schaaf, Claudia Marcolli, Martin Szelagiewicz, Beat Freiermuth
-
Patent number: 6586634Abstract: Process for the preparation of (1S,2R)-1-amino-2-indanol-(R,R)-tartrate methanol solvate, in which in a solvent a mixture of enantiomers of cis-1-amino-2-indanol reacts at an elevated temperature with (R,R)-tartaric acid and methanol and in which optically enriched (1S,2R)-1-amino-2-indanol-(R,R)-tartrate methanol solvate crystallizes out, after which the crystals are recovered, the recovery taking place at a temperature between 10 and 50° C. in the presence of 0-20 wt. % water relative to the amount of methanol plus solvent, on the understanding that if the reaction mixture is essentially free from water the recovery substantially takes place at a temperature between 30 and 50° C. Preferably the reactants are at least in part contacted with each other at an elevated temperature and only methanol is used as solvent. Preferably the amount of (1S,2R)-1-amino-2-indanol applied is between 0.02 and 0.1 g per ml of solvent.Type: GrantFiled: June 12, 1998Date of Patent: July 1, 2003Assignee: DSM N.V.Inventor: Robert Patrick Hof
-
Publication number: 20030105305Abstract: 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: ApplicationFiled: December 5, 2001Publication date: June 5, 2003Inventor: Phillipa M. Wiggins
-
Patent number: 6521792Abstract: A method for separating the diastereomer bases of 2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)-cyclohexanol in which the separation of the diastereomer bases takes place through formation of a base hydrate.Type: GrantFiled: December 21, 2001Date of Patent: February 18, 2003Assignee: Gruenenthal GmbHInventors: Bernhard Akteries, Michael Finkam
-
Patent number: 6469213Abstract: Cis-Tramadol hydrochloride is prepared by forming a Mannich hydrochloride, liberating the Mannich base, reacting the Mannich base with a Grignard reagent to form a base hydrate of cis-Tramadol which is used to form pure cis-Tramadol hydrochloride. Also claimed is the base hydrate of cis-Tramadol per se and its use as a medicament.Type: GrantFiled: January 14, 2000Date of Patent: October 22, 2002Assignee: Russinsky LimitedInventors: Helmut Schickaneder, Aggelos Nikolopoulos
-
Patent number: 6399829Abstract: (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: GrantFiled: November 20, 2000Date of Patent: June 4, 2002Assignee: Mallinckrodt Inc.Inventors: Esa T. Jarvi, Neile A. Grayson, Robert E. Halvachs
-
Patent number: 6008412Abstract: The present invention relates to processes for resolving N-methyl-3(R,S)-hydroxy-3-phenylpropylamine and N,N-dimethyl-3 (R,S) -hydroxy-3-phenylpropylamine with the isomers of mandelic acid and the resulting salts.Type: GrantFiled: March 26, 1999Date of Patent: December 28, 1999Assignee: Eli Lilly and CompanyInventor: Andrew Michael Ratz
-
Patent number: 5952528Abstract: A process for enhancing the purity of 2R-?1-hydroxy-1-trifluoromethyl-3-cyclopropylpropyn-2-yl!-4-chloroaniline comprising the formation of an acid addition salt which is capable of rejecting the racemate in the selected organic solvent.Type: GrantFiled: September 2, 1998Date of Patent: September 14, 1999Assignee: Merck & Co., Inc.Inventors: Cheng Yi Chen, Edward J. J. Grabowski, Paul J. Reider, Lushi Tan, Richard D. Tillyer
-
Patent number: 5919990Abstract: The disclosure is of a process for recovering valuable by-products of the condensation of phenol and a ketone from a mother liquor obtained for example upon crystallization of a 1:1 adduct of phenol and bisphenol, said mother liquor containing phenol, bisphenol, isomers, contaminant by-products of the condensation reaction of phenol with the ketone and acidic impurities. The mother liquor is distilled/evaporated leaving a tarry residue, which is the feedstock for the process of the invention. The recovery comprises heating the feedstock with proportions of an arylamine salt, to extract the bisphenol-A values as aminophenylhydroxylphenyl-alkanes.Type: GrantFiled: October 20, 1997Date of Patent: July 6, 1999Assignee: General Electric CompanyInventor: Parfait J.M. Likibi
-
Patent number: 5877351Abstract: A process for the isolation and purification of (RR,SS)-2-?(dimethylamino)methyl!-1-(3-methoxyphenyl)cyclohexanol and its salts from a Grignard reaction mixture which includes the (RR,SS) isomer, the (RS,SR) isomer and Grignard reaction side products. An aqueous solution of HBr is added to the reaction mixture to effect the selective precipitation of the (RR,SS) hydrobromide isomer from the mixture while the (RS,SR) isomer remains in solution. The precipitated (RR,SS)-2-?(dimethylamino)methyl!-1-(3-methoxyphenyl)cyclohexanol hydrobromide is converted to (RR,SS)-2-?(dimethylamino)methyl!-1-(3-methoxyphenyl)cyclohexanol hydrochloride.Type: GrantFiled: December 24, 1997Date of Patent: March 2, 1999Assignee: Wyckoff Chemical Company, Inc.Inventor: Kenneth E. Anderson
-
Patent number: 5863952Abstract: The single enantiomers of formula (I) and salts thereof ##STR1## are calcium channel antagonists useful in the treatment of ischaemic conditions e.g., stroke.Type: GrantFiled: July 11, 1997Date of Patent: January 26, 1999Assignee: SmithKline Beecham plcInventors: Barry Sidney Orlek, John David Harling
-
Patent number: 5856579Abstract: A process for optical resolution of a racemic substituted benzylamine is provided that involves reacting the racemic substituted benzylamine in a solvent with an optically active N-acyl-phenylalanine, -aspartic acid, or -glutamic acid, and separating the diastereomers formed by making use of the difference in the mutual solubilities of the two diastereomer salts which are generated therein.Type: GrantFiled: October 15, 1996Date of Patent: January 5, 1999Assignee: Ajinomoto Co., Inc.Inventors: Tadashi Takemoto, Toyoto Hijiya, Teruo Yonekawa
-
Patent number: 5679857Abstract: L-amino acid amides are converted to the corresponding D-amino acid amides. An amide formed from an L-amino acid and an optically active (S)-.alpha.-alkylbenzylamine is subjected to dehydration condensation with an aryl aldehyde to form a Schiff's base, which is racemized at the amino acid moiety in the presence of a base to yield an N-allylidene-D-amino acid-(S)-amide. The less-soluble diastereomer N-allylidene-D-amino acid-(S)-amide is crystallized from the reaction mixture and recovered by means of solid/liquid separation. The N-allylidene form is readily hydrolyzed into the amino acid-(S)-amide and the starting aldehyde.Type: GrantFiled: November 16, 1995Date of Patent: October 21, 1997Assignee: Ajinomoto Co., Inc.Inventors: Toyoto Hijiya, Chiaki Mochizuki, Tadashi Takemoto
-
Patent number: 5672755Abstract: The invention provides a process for the purification and isolation of (RR,SS)-2-dimethylaminomethyl-1-(3-methoxyphenyl)cyclohexanol from mixtures also containing the (RS,SR) isomer comprising reacting the above mixture in a solvent at elevated temperature under acidic conditions, whereby the (RS,SR) isomer is selectively converted to the (RR,SS) isomer, 1-(3-methoxyphenyl)-2-dimethylaminomethylcyclohex-6-ene, 1-(3-methoxyphenyl)-2-dimethyl-aminomethylcyclohex-1-ene or a mixture thereof, selectively precipitating the desired (RR,SS) isomer as an amine acid salt, and recrystallizing the purified product.Type: GrantFiled: November 14, 1996Date of Patent: September 30, 1997Assignee: Chemagis Ltd.Inventors: Ori Lerman, Michael Tennenbaum, Erez Gal, Joseph Kaspi
-
Patent number: 5629450Abstract: To produce optically active .alpha.-arylalkylamine from optically impure .alpha.-arylalkylamine.Optically impure .alpha.-arylalkylamine is mixed with optically active N-acyl-aspartic acid or glutamic acid in a solvent and the resulting two types of diastereomer salts are optically resolved utilizing difference in solubility.Type: GrantFiled: March 21, 1995Date of Patent: May 13, 1997Assignee: Ajinomoto Co., Inc.Inventors: Toyoto Hijiya, Teruo Yonekawa, Tadashi Takemoto
-
Patent number: 5414129Abstract: A process for the improved purification and separation of trans 2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol hydrochloride from a reaction mixture containing the trans isomer, the cis isomer and Grignard reaction side products, comprising combining the mixture with a solution of hydrochloric acid in a low molecular weight alcohol or with gaseous hydrogen chloride in the presence of an organic solvent selected from medium molecular weight alcohols, ketones, esters and ethers or aromatic ethers, to effect the selective precipitation of trans 2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol hydrochloride.Type: GrantFiled: September 8, 1993Date of Patent: May 9, 1995Assignee: Chemagis, Ltd.Inventors: Stephen Cherkez, Ori Lerman, Michael Tennenbaum, Hasalia Avner, Tamar Kunyevski
-
Patent number: 5306826Abstract: 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: GrantFiled: February 15, 1991Date of Patent: April 26, 1994Assignee: Stamicarbon B.V.Inventor: Wilhelmus H. J. Boesten
-
Patent number: 5284975Abstract: A method of preparing an .alpha.-d-phenylalkylbenzyl carbinol by the reaction of a phenylbenzyl ketone with an alkali metal enolate of an amide to form an aldol adduct, which is reduced and purified to form an .alpha.-d-phenylalkylbenzyl carbinol, wherein the carbinol so produced possesses analgesic activity. In an embodiment of the invention, a phenylbenzyl ketone is reacted with an alkali metal enolate of an amide to form an aldol adduct, which is reacted with an alkali metal salt of a secondary amine to form a dianion; the dianion is alkylated with an alkyl halide to form an .alpha.-isomer of an aldol adduct, which is reduced and purified to form an .alpha.-d-phenylalkylbenzyl carbinol possessing analgesic activity.Type: GrantFiled: October 8, 1992Date of Patent: February 8, 1994Assignee: Mallinckrodt Specialty Chemicals CompanyInventor: Jacob Mathew
-
Patent number: 5082970Abstract: A novel process for converting trans-isomeric N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthaleneamine to cis-isomeric N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthaleneamine is disclosed. The process involves contacting trans-isomeric N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthaleneamine, or a mixture of same with up to about an equal part by weight of the corresponding cis-isomer, with a basic equilibration agent like potassium tert.-butoxide in a reaction-inert polar organic solvent to ultimately afford a cis/trans-mixture wherein the amount of cis-amine present in said mixture achieves a constant value of about 2:1 on a weight-by-weight basis. The aforesaid resultant mixture is useful as an intermediate product that ultimately leads to pure cis-(1S) (4S)-N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthaleneamine (sertraline), which is a known antidepressant agent.Type: GrantFiled: March 6, 1991Date of Patent: January 21, 1992Assignee: Pfizer Inc.Inventor: Tamim F. Braish
-
Patent number: 4652563Abstract: This invention relates to dihydropyridazinone compounds having a cyclopropylmethoxyethyl group in the 6-substituent. These compounds are vasodilators and .beta.-adrenoceptor antagonists. A particular compound of the invention is 6-[4-[3-[2-hydroxy-3-[4-(2-(cyclopropylmethoxy) ethyl)phenoxy]propylamino]propionamido]phenyl]-5-methyl-4,5-dihydro-3 (2H)-pyridazinone.Type: GrantFiled: May 16, 1985Date of Patent: March 24, 1987Assignee: Smith Kline & French Laboratories Ltd.Inventor: Robert A. Slater
-
Patent number: 4489209Abstract: A process of separating amines having different basicity constants is disclosed. The more reactive amine is converted to a salt which is extracted with water in a multiple stage countercurrent extractor. The salt form of the amine is converted to the free amine. In a preferred aspect of the invention the amine salt is an amine sulfite which can be converted to free amine and sulfur dioxide. The sulfur dioxide can be reused to generate more amine sulfite. The more reactive amine is then separated from the water and part of it recovered. The remainder of the more reactive amine is recycled to the countercurrent extractor. The less reactive amine is removed from the countercurrent extractor in the free amine state as an organic phase along with any organic solvent that is used. Part of the less reactive amine is recovered from the system while the remainder is converted to a salt and an aqueous solution thereof recycled to the countercurrent extractor.Type: GrantFiled: December 17, 1981Date of Patent: December 18, 1984Assignee: E. I. Du Pont de Nemours and CompanyInventor: Tzu-Ching Chang