cas 136434-34-9, Duloxetine hydrochloride | Articles data

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An Improved Process for Synthesis of (S)-Duloxetine Hydrochloride Involving Enzymatic Asymmetric Carbonyl Reduction on a Novel Ketoamine
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Sasane, Sachin A.,Husain, Mofazzal,Bhise, Nandu B.,Singh, Girij P.,Joseph, Alex,Shenoy, Gautham G.
p. 1 - 8
(2020/11/02)

Preparation method of S-(+)duloxetine hydrochloride intermediate
The invention discloses a preparation method of a compound of a formula B (shown in the description). The preparation method comprises the steps of dissolving a compound of a formula A (shown in the description) in a solvent, and reacting under the effect of a reducing agent. Furthermore, the ee value of the compound of the formula B obtained by reducing in the presence of a complex, namely ferrocene, is over 98%. The preparation method provided by the invention is simple and feasible, the resolution or the chiral catalysis induction is not required, the product yield and the chiral purity arehigh, and the preparation method is suitable for the industrial production of S-(+)duloxetine hydrochloride intermediate.
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Paragraph 0100-0102

(2019/04/09)

Preparation method for duloxetine salified hydrochloride
The invention discloses a preparation method for duloxetine salified hydrochloride, and particularly relates to a reaction for the duloxetine salified hydrochloride. The reaction comprises the following steps: using duloxetine as a reactant, adding organic solution of hydrogen chloride into duloxetine solution for reacting, while a pH value is adjusted to be 7-8, stopping adding the organic solution of hydrogen chloride until a solid is separated out, continuously adding the organic solution of hydrogen chloride, and reacting until the pH is 3-4. The salifying method is moderate in reaction conditions, simple in operation, high in product purity and optical purity, and good in inter-batch quality stability, and suitable for the industrialized production.
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Paragraph 0030-0034

(2018/10/11)

Anti-depression of the raw material preparation method
The present invention discloses an anti-depression drug duloxetine hydrochloride - process improvement and optimization, which belongs to the field of biological medicine. Comprises the following main features: a) used in the Mannich reaction in N - methyl benzylamine hydrochloride, without the use of dimethylamine hydrochloride, so that the follow-up steps in the dealkylation reaction effect is better, yield is higher; b) without using any expensive chiral catalyst or a phase transfer catalyst, to use with high stability and high catalytic performance of metal catalyst; c) the better solvent for crystallization and to the solvent method, to avoid the harm of the residual solvent for crystallization; d) splitting the chiral compound in the dealkylation after, adopts a unique recrystallization technology, will split the mixture after separation, purity and relatively easy to assemble and disassemble the luminosity (S)- N - methyl - 3 - (1 - naphthoxy) - 3 - (2 - thienyl) propylamine/tartrate, so that the resulting duloxetine hydrochloride product can achieve a better therapeutic effect. The process of the invention clear, simple and convenient operation, mild reaction conditions, low production cost, is extremely beneficial to industrial production.
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(2018/07/15)

Duloxetine hydrochloride salt of basic and duloxetine (by machine translation)
[Problem] to suppress toxic byproducts, and suppressing the formation of decomposition products of high purity optical isomers as well as the method for manufacturing a basic duloxetine hydrochloride duloxetine. [Solution] a basic manufacturing method of duloxetine, [...], potassium hydroxide and toluene in the presence of alcohol in the mixing step, and, by heating the reaction mixture obtained, comprising the step of distilling off the solvent in the reaction portion, a basic manufacturing method of duloxetine. [Drawing] no (by machine translation)
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(2017/06/02)

Preparation of duloxetine hydrochloride
The invention belongs to the fields of organic chemistry and pharmaceutical chemistry, and particularly relates to a synthesis technique of duloxetine hydrochloride. By converting the R configuration compound into S configuration, compared with the duloxetine hydrochloride prepared from the single S-configuration compound, the total yield is enhanced by nearly 47%, and the production cost is lowered. 1-chloroethylchloroformate is used instead of phenyl chloro-formate to directly generate the duloxetine hydrochloride during demethylation, thereby reducing the salification step, shortening the production cycle and saving the cost.
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Paragraph 0061-0062; 0070-0071

(2017/08/26)

Method for the synthesis of duloxetine
A synthetic method of duloxetine is as below: reacting water, tetrahydrofuran or dioxane, 1-chloro ethyl-N-methyl-((S)-3-(naphthalene-1-phenoxy)-3-(thiophene-2-yl) propyl) carbamate and alkali at a reflux temperature of 20 DEG C, preferably 50 DEG C; after the reaction, condensing a reaction liquid; and adding another organic solvent for extraction, so as to obtain a solution containing dutoxetine. Compared with the existing method for preparing duloxetine, the method overcomes the disadvantages of long reaction time or high reaction temperature, high energy consumption, long production cycle, low yield, a large amount of industrial waste water difficult to process, harm to the environment, flammable and explosive reagents and huge security hidden trouble, and has the advantages of low reaction temperature, short reaction time, a small amount of produced industrial waste liquid, greenness, environment-friendliness, high safety, and suitability for large-scale industrial production of duloxetine.
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(2016/10/07)

A method for preparing duloxetine hydrochloride
The invention provides a method for preparing duloxetine hydrochloride. The method comprises the following steps: dripping a compound III in sodium hydroxide to react to prepare a compound II; adding the compound II into solid ammonium chloride in batches to prepare duloxetine hydrochloride; washing with cold diethyl ether; crystallizing with acetone to prepare duloxetine hydrochloride with high purity and high yield. Compared with the prior art, the method has the advantages that the reaction time is greatly shortened, in the literature is shortened from 18-70 hours to 2-4 hours. Furthermore, the duloxetine hydrochloride prepared by the method is more convenient and more practical, and the yield is high; the duloxetine hydrochloride is washed with cold diethyl ether, and is crystalized with acetone, so that the duloxetine hydrochloride can be precipitated more easily, is high in purity and is not needed to be recrystallized, and loss is avoided. The synthesis method is easier and more practical, the production efficiency is greatly improved, the production cost is reduced, and the total yield of duloxetine hydrochloride synthesized from an initial raw material 2-acetylthiophene can be over 17 percent.
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Paragraph 0032

(2017/03/08)

OLIGOMER-ARYLOXY-SUBSTITUTED PROPANAMINE CONJUGATES
The invention relates to (among other things) oligomer- aryloxy-substituted propanamine conjugates and related compounds. A conjugate of the invention, when administered by any of a number of administration routes, exhibits advantages over un-conjugated aryloxy-substituted propanamine compounds.
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Paragraph 0245; 0253

(2016/11/17)

PROCESS FOR THE PREPARATION OF HIGHLY PURE DULOXETINE HYDROCHLORIDE
The present invention relates to an improved process for the preparation of Duloxetine and pharmaceutical acceptable salts or derivatives thereof, in particular to a process for large scale production of Duloxetine hydrochloride in high yield and high enantiomeric and chemical purity.
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Paragraph 5

(2013/05/09)

SYNTHESIS OF DULOXETINE AND/OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
The invention describes an improved process for the synthesis of duloxetine and/or pharmaceutically acceptable salts thereof enabling preparation of duloxetine and/or pharmaceutically acceptable salts thereof with high chemical and enatiomeric purity. The process includes addition of an organic acid in the phase of formation of a duloxetine salt with an acid, preferably in the form of hydrochloride, and optionally in the phase of recrystallization of the formed duloxetine salt, wherein an organic acid is preferably selected from the group comprising formic acid, acetic acid, propanoic acid, butanoic acid or any mixtures thereof, more preferably acetic acid.
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Page/Page column 23

(2011/11/01)

AN IMPROVED PROCESS FOR THE PREPARATION OF DULOXETINE HYDROCHLORIDE
The present disclosure provides solution to the problem associated in the preparation of duloxetine hydrochloride. This disclosure is successful in preventing the racemization and thereby prevents the formation of unwanted isomer of duloxetine hydrochloride. In addition, the disclosure provides a simple technique for removal of unreacted reactant, 1-fluoronapthalene used as a reactant in the process to obtain (S)-(+)-N-methyl-3(1-naphthalenyloxy)-3-(2-thienyl)propanamine hydrochloride, compound of formula (VI).
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(2011/07/09)

IMPROVED PROCESS FOR THE PREPARATION OF DULOXETINE AND ITS PHARMACEUTICALLY ACCEPTABLE SALT
The present invention relates to an improved process for racemizing one of the enantiomers, or an enantiomerically enriched mixture, of an optically active compound (S)-N, N-dimethyl-3-(2-thienyl)-3-hydroxypropanamine, a key intermediate used for the preparation of (S)-N-methyl-3-(1-naphthalenyloxy)-3-(2- thienyl) propanamine (duloxetine) or its hydrochloride salt. Moreover, the present invention also relates to an improved process for the preparation of (S)-N-methyl-3- (1-naphthalenyloxy)-3-(2-thienyl) propanamine (duloxetine) or its hydrochloride salt having low content of undesired R-isomer and chiral purity not less than 99%.
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Page/Page column 24-25

(2011/04/19)

A METHOD OF CRYSTALLIZATION OF (S)-N-METHYL-3-(1-NAPHTHYLOXY)-3- (2-THIENYL)PROPYLAMINE HYDROCHLORIDE (DULOXETINE)
(S)-N-Methyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine hydrochloride of formula (I) is crystallized in such a way that suspension of duloxetine in a mixture of an aprotic solvent and a protic solvent is stirred at an increased temperature under simultaneous reduction of the volume proportion of the protic solvent.
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Page/Page column 9

(2011/04/14)

METHOD FOR THE PREPARATION OF N-METHYL-ARYLOXY-PROPANAMINE DERIVATIVES
The present invention is related to a method for the preparation of N-methyl-aryloxy-propanamine derivatives, which comprises reacting a suitable uretane derivative of the Formula (XXIV) with a Grignard reagent.
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Page/Page column 37-38

(2010/04/03)

A PROCESS FOR THE PREPARATION OF DULOXETINE HYDROCHLORIDE
The present invention relates to a process for the preparation of Duloxetine hydrochloride of formula (I).
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Page/Page column 6

(2010/10/03)

PREPARATION OF DULOXETINE AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS BY THE USE OF ASYMMETRIC TRANSFER HYDROGENATION PROCESS
The invention deals with the preparation of duloxetine or its pharmaceutically acceptable salts with high enantiomeric and chemical purity via beta-keto amines wherein the amino group is optionally protected and the subsequent asymmetric transfer hydrogenation using chiral Ru- or Rh-catalyst to the corresponding alcohol.
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Page/Page column 23-24

(2010/04/03)

AN IMPROVED PROCESS FOR THE PREPARATION OF DULOXETINE AND SALTS THEREOF
The present invention relates to improved process for the preparation of Duloxetine of formula (I) and salts thereof wherein said improvement takes place in step of condensation.
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Page/Page column 8-9

(2010/08/04)

METHOD FOR THE PREPARATION OF DULOXETINE HYDROCHLORIDE
The present invention relates to an improved process for the preparation of Duloxetine and its intermediates (S)-(+)-N,N-dimethyl-3-(1-naphthalenyloxy)-3-(2-thienyl)propanamine by reacting (S)-(+)-N,N-dimethyl-3-(2-thienyl)-3-hydroxypropanamine with 1-fluoronaphthalene in the presence of a base; wherein the improvement lies in conducting the reaction in the absence of solvent.
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Page/Page column 4

(2010/11/03)

POLYMORPHIC FORM OF DULOXETINE HYDROCHLORIDE
The present invention relates to Form I of duloxetine hydrochloride and its preparation.
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Page/Page column 2

(2010/11/03)

NOVEL PROCESS FOR PREPARATION OF DULOXETINE AND INTERMEDIATES FOR USE THEREIN
A novel process for the preparation of substantially (S)-(+)-N-methyl-3-(l-naphthalenyloxy)- 3-(2-thiophenyl) propanamine hydrochloride comprising formation of lewis acid salt of (S)- (+)-N-methyl-3-(l-naphthalenyloxy)-3-(2-thiophenyl) propanamine and (S)-(+)-N,N- dimethyl-3-(l-naphthalenyloxy)-3-(2-thiophenyl) propanamine to remove the R isomer of (S)-(+)-N-methyl-3-(l-naphthalenyloxy)-3-(2-thiophenyl) propanamine and (S)-(+)-N,N- dimethyl-3-(l-naphthalenyloxy)-3-(2-thiophenyl) propanamine avoiding removing R isomer impurity without resolution through formation of chiral salt.
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Page/Page column 19

(2009/10/22)

SYNTHESIS AND PREPARATIONS OF DULOXETINE SALTS
The invention relates to an improved process for the preparation of duloxetine hydrochloride.
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Page/Page column 5

(2009/04/24)

PROCESS FOR THE PREPARATION OF 3-ARYLOXY-3-ARYLPROPANAMINES
The present invention provides a process for the preparation of 3-aryloxy-3-arylρropanamine derivatives. Particularly the present invention provides a process for the preparation of duloxetine and pharmaceutically acid addition salts thereof specifically, duloxetine hydrochloride of formula (I), using 3-O-protected propanolamine derivatives. The invention also aims at providing a process for the preparation of highly pure duloxetine hydrochloride of formula (I) from duloxetine free base via its acid addition salts The invention further aims at providing a process for the purification of duloxetine hydrochloride, wherein the level of unwanted R-enantiomer is reduced to nearly 0%.
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Page/Page column 26-27

(2009/04/25)

PREPARATION OF DULOXETINE AND ITS SALTS
The present patent application relates to a process for the preparation of Duloxetine and its salts comprising reacting (S) - (+)-N, N-Dimethyl-3-(2- thienyl)-3-hydroxypropanamine or a salt there of with 1-fluoronapthalene in the presence of sodium hydride and potassium 4-methyl benzoate; N- demethylation via formation of phenylcarbamate to obtain Duloxetine which may then converted in to a pharmaceutically acceptable salt.
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Page/Page column 13

(2009/12/05)

Process for the preparation of enantiomerically pure 3-hydroxy-3-arylpropylamines and their optical stereoisomers
The invention provides a process for the preparation of enantiomerically pure 3-hydroxy-3-arylpropylamines via novel semiester derivatives containing o-carboxy benzoyl group as intermediates. The 3-hydroxy-3-arylpropylamines serve as precursor for the preparation of serotonin or noradrenalin reuptake inhibitors such as duloxetine, atomoxetine, fluoxetine, nisoxetine and norfluoxetine.
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Page/Page column 8

(2009/06/27)

Gastro-resistant pharmaceutical oral compositions comprising duloxetine or its pharmaceutically acceptable derivatives
The present invention relates to a pharmaceutical composition comprising an active core comprising duloxetine or its pharmaceutically acceptable derivatives, a separating layer comprising a water soluble alkaline substance and a gastro-resistant coating comprising a gastro-resistant polymer selected from methacrylic acid copolymers and optionally an over-coating layer.
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(2009/12/27)

Process for the preparation of pure duloxetine hydrochloride
The present invention relates to a process for the preparation of pure Duloxetine hydrochloride. The present invention further relates to duloxetine hydrochloride substantially free of residual hydrochloric acid.
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Page/Page column 4-5

(2009/10/18)

PROCESS FOR THE PREPARATION OF PURE DULOXETINE HYDROCHLORIDE
The present invention relates to a process for the preparation of pure Duloxetine hydrochloride. The present invention further relates to duloxetine hydrochloride substantially free of residual hydrochloric acid.
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Page/Page column 2-3

(2009/12/02)

A METHOD FOR THE PREPARATION OF DULOXETINE HYDROCHLORIDE
The present invention relates to an improved process for the preparation of Duloxetine and its intermediates (S)-(+)-N,N-dimethyl-3-(l-naphthalenyloxy)-3-(2- thienyl)propanamine by reacting (S)-(-)-N,N-dimethyl-3-(2-thienyl)-3-. hydroxypropanamine with 1-fluoronaphthalene in the presence of a base; wherein the improvement lies in conducting the reaction in the absence of solvent.
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Page/Page column 8-9

(2009/09/04)

A METHOD OF PURIFICATION OF (S)-N-METHYL-3-(1-NAPHTYLOXY)-3-(2-THIENYL) PROPYLAMINE HYDROCHLORIDE (DULOXETINE)
A method of purification of (5)-7V-methyl-3-(l-naphtyloxy)-3-(2-thienyl) propylamine hydrochloride of formula I, comprising (a) transformation of the substance of formula I to its free base by the action of an organic or inorganic base in an aqueous environment; and (b) transformation of the base of the substance of formula I to crystalline hydrochloride by the action of hydrochloric acid or gaseous HCl in an organic solvent or a mixture of organic solvents. A method of purification of (S)-N-methyl-3-(l-naphtyloxy)-3-(2-thienyl) propylamine hydrochloride of formula I, comprising dissolution of this substance in a minimum quantity of methanol containing 0 to 50% of water and its transformation back to the solid phase (precipitation) by addition of a less polar solvent.
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Page/Page column 6

(2008/12/06)

A PROCESS FOR THE PREPARATION OF DULOXETIN AND NEW KEY INTERMEDIATES FOR USE THEREIN
The present invention relates to a process for the preparation of duloxetin. ((S)-(+)-N-methyl-N-(3-(l-naρhthalenyloxy)-3-(2-thienyl)propanamine) of formula (I) and pharmaceutically acceptable salts thereof, said process comprising the steps of a) resolving racemic 3-(N-methyl-N-berizylamino)-1-(2-thienyl)-1-propanol of formula (II) with a D-phenylglycine derivative to obtain a compound of formula (IV); and b) reacting (S)-3-(N-methyl-N-ben2yIamino)-1-(2-thienyl)-1-propanol of formula (IV) with 1-fluoronaphthalene to yield (S)-N-methyl-N-benzyl-3-(1-naphthalenyloxy)-3-(2- thienyl)propanamine of formula (V), reacting the compound of formula (V) obtained with 1-chloroethyl chloroformate to yield duloxetin of formula (I), and if desired converting the duloxetin of formula (I) obtained into an acid addition salt thereof.
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Page/Page column 23

(2008/12/06)

A PROCESS FOR PREPARATION OF (S)-(+)-N-METHYL-3(1-NAPHTHYLOXY)-3(2-THIENYL)PROPYLAMINE HYDROCHLORIDE
The present invention provides an improved process for preparation of intermediate of Duloxetine base and hydrochloride salt thereof.
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Page/Page column 17

(2008/12/07)

PROCESS FOR PREPARING DULOXETINE HYDROCHLORIDE
Enantiomerically pure S-(+)-duloxetine hydrochloride with high purity as determined by area percentage of HPLC are disclosed. Also disclosed are improved process for preparing duloxetine hydrochloride of formula (I).
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Page/Page column 36-37

(2008/12/07)

Process for the Preparation of 1-Naphthol Mixed Ethers and Intermediates of Crystalline Forms of (+) and (-)-Duloxetine
The invention relates to a process for the preparation of duloxetine (1a), comprising the reaction between 1-fluoronaphthalene and 3-N,N-dimethylamino-1-(2-thienyl)-propan-1-ol in the presence of 1,3-dimethyl-2-oxo-hexahydropyrimidine (DMPU) as the solvent; a method for the identification of duloxetine enantiomers and for the determination of its optical purity is also disclosed.
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Page/Page column 3

(2008/12/09)

NOVEL PROCESS FOR PREPARATION OF DULOXETINE HYDROCHLORIDE
An improved, safer and easy to operate on plant scale process for synthesis of duloxetine hydrochloride (1) having chiral purity greater than 99.9% that is characterized by the following: (i) preparation of racemic condensed compound (RS)-N,N-di methyl-3- (1-naphthyloxy)-3-(2-thienyl)propanamine (4) by reaction of racemic hydroxy compound (2) with 1-fluronaphthalene (3) in presence of a base such as sodamide, potassium amide or potassium bis(trimethylsilyl)amide (KHDMS) in polar aprotic solvent, (ii) optical resolution of racemic condensed compound (5a + 5b) with di-benzoyl-L-tartaric acid (7, DBTA, R = H) or di-para-anisoyl-L-tartaric acid (7, DATA, R = OCH3) to obtain crude (S)-N.N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propanamine dibenzoyl tartarate salt (8a) or (S)-N.N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propanamine di-p-anisoyl tartarate salt (9a) respectively, (iii) optionally purification of crude tartarate salts (8a or 9a) by crystallization, (iv) optionally purification of duloxetine hydrochloride (1) by crystallization and (v) racemization of undesired (R)-N,N-di methyl-3-(1-naphthyloxy)-3-(2-thienyl)propanamine (5b) by treatment with base potassium bis(trimethylsilyl)amide (KHDMS) to obtain racemic mixture of condensed compounds (5a and 5b). A novel salt S(+)-N.N-dimethyl-3-(1-naphthylenyloxy)-3-(2-thienyl)propanamine dibenzoyl -(L)- tartarate (8a) and S(+)-N.N-dimethyl-3-(1-naphthylenyloxy)-3-(2-thienyl)propanamine di-p-anisoyl-(L)- tartarate (9a). Novel process for racemization of undesired (R)-N,N-di methyl-3-(1-naphthyloxy)-3-(2-thienyl)propanamine (5b) by treatment with KHDMS to obtain racemic mixture condensed compounds (5a and 5b).
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Page/Page column 25

(2008/12/07)

PROCESSES FOR THE PREPARATION OF CRYSTALLINE FORMS OF DULOXETINE HYDROCHLORIDE
The present invention also pertains to processes for the preparation of form A and form T, which involves dissolving duloxetine hydrochloride in particular solvents and cooling the solution to obtain crystals that are dried.
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Page/Page column 21-22

(2008/06/13)

PROCESS FOR THE PREPARATION OF DULOXETINE
The invention relates to a process for the preparation of duloxetine (1a), comprising the reaction between 1-fluoronaphthalene and 3-N,N-dimethylamino-l-(2-thienyl)-propan-l-ol in the presence of l,3-dimethyl-2-oxo-hexahydropyrimidine (DMPU) as the solvent; a method for the identification of duloxetine enantiomers and for the determination of its optical purity is also disclosed.
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Page/Page column 7

(2008/06/13)

DNT-FUMARATE AND METHODS OF PREPARATION THEREOF
(S)-N,N-Dimethyl-3-(l-naphthalenyloxy)-3-(2-thienyl)propanamine fumarate (DNT-fumarate) and polymorphs of DNT-fumarate, compositions of DNT-fumarate and its polymorphs, processes for the preparation of DNT-fumarate and its polymorphs, and processes for the preparation of duloxetine hydrochloride from DNT-fumarate are provided.
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Page/Page column 16

(2008/06/13)

DNT-MALEATE AND METHODS OF PREPARATION THEREOF
(S)-N,N-Dimethyl-3-(l-naphtlialenyloxy)-3-(2-thienyl)propanamine nialeate (DNT-maleate) and polymorphs of DNT-maleate, compositions of DNT-maleate and its polymorphs, processes for the preparation of DNT-maleate and its polymorphs, and processes for the preparation of duloxetine hydrochloride from DNT-maleate are provided.
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Page/Page column 20

(2010/11/26)

DNT-succinate and methods of preparation thereof
(S)-N,N-Dimethyl-3-(1-naphthalenyloxy)-3-(2-thienyl)propanamine succinate (DNT-succinate) and polymorphs of DNT-succinate, compositions of DNT-succinate and its polymorphs, processes for the preparation of DNT-succinate and its polymorphs, and processes for the preparation of duloxetine hydrochloride from DNT-succinate are provided.
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Page/Page column 7

(2010/11/28)

DULOXETINE SALTS
The subject of the present invention is the provision of new salts of duloxetine of the Formula (I) with organic acids, process for their preparation and medicinal products containing thereof. The new salts are essetially free from the impurity of the Formula (II) and possess high purity and high stability. The new duloxetine salts are prepared by reacting duloxetine free base dissolved in an organic solvent with an approximately equimolar amount of an organic acid. Particularly advantageous crystalline salts are those formed with fumaric acid, citric acid or (-)-mandelic acid.
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Page/Page column 28-29

(2008/06/13)

A METHOD FOR THE PREPARATION OF (S)-N-METΗYL-3-(l-NAPHTHYLOXY)-3-(2-THIENYL)PROPYLAMINE HYDROCHLORIDE (DULOXETINE)
A method of preparation of (S)-N-methyl-3-(l-naphthyloxy)-3-(2-mienyl)propylamine of Formula(I) and its pharmaceutically acceptable salts, comprising a) reaction of (RS)-N,N-dimethyl-3-(l-naphthyloxy)-3-(2-thienyl)propylamine of formula (III) with optically active D-tartaric acid or an acid salt derived from D-tartaric acid forming a mixture of diastereoisomeric salts of N,N-dimethyl-3-(l-naphthyloxy)- 3-(2-thienyl)propylamine and D-tartaric acid (2:1), b) isolation of the salt (S)-N,N-dimethyl-3-(naphthyloxy)-3-(2- thienyl)propylamine/D-tartrate (2:1) from the mixture of diastereoisomeric salts in an organic solvent, water or a mixture thereof and release of (S)-N,N-dimethyl-3-(l- naphthyloxy)-3-(2-thienyl)ρropylamine of formula (S)-(III) by action of an inorganic or organic base, c) demethylation of (S)-N,N-dimethyl-3-(l-naphthyloxy)-3-(2-thienyl)propylamine by action of an alkylchloroformate of formula ClCOOR (R = C1 - C5 alkyl, or C6 - C12 aryl or alkylaryl), especially phenyl, ethyl or methyl chloroformate, and d) hydrolytic release of the duloxetine base of formula (I) and optionally conversion of the base to a salt with the respective acid, or salt of a weak base, wherein one uses, as the optically active substance in step (a), D-tartaric acid in the molar ratio 1:2 relative to the substance of formula (III), or an alkali metal acid D-tartrate or ammonium tartrate, or alternatively alkylammonium tartrate of formula (IV) in the molar ratio 1:1 relative to the substance of formula (III).
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Page/Page column 10

(2008/06/13)

CRYSTALLINE DULOXETINE HYDROCHLORIDE
Crystalline duloxetine hydrochloride, compositions containing the same and methods for the production thereof.
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Page/Page column 13

(2008/06/13)

CRYSTALLINE DULOXETINE HYDROCHLORIDE
Crystalline duloxetine hydrochloride, compositions containing the same and methods for the production thereof.
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Page/Page column 7

(2008/06/13)

A process for the preparation of an intermediate useful for the asymmetric synthesis of (+)duloxetine
A process for the preparation of (+)duloxetine, or an acid addition salt thereof, comprising: (i) Resolving racemic (±)N-methyl duloxetine with a less than stoichiometric amount of a chiral acid in combination with suitable amounts of a hydrohalogen acid to give a salt of the chiral acid and (+)N-methyl duloxetine, substantially free from (-)N-methyl duloxetine; (ii) Demethylating the (+)N-methyl duloxetine prepared in step (i) to give (+)duloxetine or another acid addition salt in enantiomerically pure form.
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Page/Page column 5-6

(2010/11/28)

IMPROVED PROCESS FOR PURE DULOXETINE HYDROCHLORIDE
A process for the preparation of pure Duloxetine hydrochloride comprises the steps of : a) reacting 1-(thiophen-2-yl)ethanone with dimethylamine hydrochloride, b) purifying the component in a solvent, c) reducing the component with an alkali metal borohydride, d) resolving the compound with a chiral acid, and treating the obtained compound with weak inorganic base, e) reacting the compound to give Duloxetine oxalate salt and f) converting the Duloxetine salt into its hydrochloride salt. Further the purifications of the obtained compound and of two intermediate products are described.
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Page/Page column 18

(2008/06/13)

Crystalline forms of duloxetine hydrochloride and processes for their preparation
The present invention relates to polymorphic forms of duloxetine hydrochloride, especially (duloxetine HCl), which are characterized by an X-ray diffraction pattern with peaks (2θ):9.6, 13.9, 18.0, 18.8, 19.2, 20.8, 27.4, 27.9 (designated form A) or an X-ray diffraction pattern with characteristic peaks (2θ): 12.0, 14.8, 19.8, 21.3, 21.6, 22.1, 22.4, 23.1, 24.1 (designated form T). The present invention also pertains to processes for the preparation of form A and form T, which involves dissolving duloxetine hydrochloride in particular solvents and cooling the solution to obtain crystals, that are dried.
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Page/Page column 10

(2008/06/13)

DULOXETINE HCL POLYMORPHS
A crystalline form of duloxetine hydrochloride, pharmaceutical compositions of the crystalline form of duloxetine hydrochloride, and methods of preparing the crystalline form of duloxetine hydrochloride are provided.
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Page/Page column 9-10

(2008/06/13)

A NOVEL PROCESS FOR THE PREPARATION OF (S)-(+)-N,N-DIMETHYL-3-(1-NAPHTHALENYLOXY)-3-(2-THIENYL)PROPANAMINE, A DULOXETINE INTERMEDIATE
Provided is a process for preparing a duloxetine intermediate,(S)-(+)-N,N-Dimethyl-3-(1- naphthalenyloxy)-3-(2-thienyl)propanamine (DNT), and its conversion to duloxetine or a pharmaceutically acceptable salt thereof.
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Page/Page column 11

(2010/11/28)

2-(N-METHYL-PROPANAMINE)-3-(2-NAPHTHOL) THIOPHENE, AN IMPURITY OF DULOXETINE HYDROCHLORIDE
The invention encompasses 2-(N-methyl-propanamine)-3-(2-naphthol) thiophene, a duloxetine hydrochloride impurity, as well as its use as a reference marker and reference standard.
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(2008/06/13)