cas 116539-59-4, Duloxetine | Articles data

Articles about 116539-59-4Total 62 be found

Article title
Article abstract
Author
Journal number and time
Download

Preparation method of duloxetine
To the method, 1 - naphthol and 3 - (2 - thienyl) -2 - acrolein serve as starting materials, and (S)-3 - (1 - naphthyloxy) -3 - (2 - thienyl) propanal is obtained through addition reaction under the action of a catalyst. The raw materials are cheap and easily available, and 1 - fluoronaphthalene which is expensive is not needed. Sodium hydride and operation are tedious, the cost is low, the process operation is safe and convenient, the three wastes are small in generation amount, and green and environment-friendly. The reaction atom economy is high, the reaction selectivity of each step is high, the side reaction is small, the optical purity and yield of the target product are high, and the green industrial production is facilitated.
-
(2021/09/26)

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

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)
-
Paragraph 0052-0054

(2017/06/02)

Preparation method for chiral gamma-sec-amino-alcohol
The invention provides a preparation method for chiral gamma-sec-amino-alcohol. The preparation method is characterized in that an acid addition salt of beta-sec-amino-ketone as shown in a general formula (I) which is described in the specification, alkali, a metal salt additive and a bisphosphine-rhodium complex are added into a solvent and a reaction is carried out in a hydrogen atmosphere so as to produce a chiral gamma-sec-amino-alcohol compound as shown in a general formula (II) which is described in the specification; and in the general formula (I) and the general formula (II), Ar represents an aryl group with or without substituent, R represents an alkyl group or aralkyl group, and HY represents acid. The preparation method is simple in synthesis route and process; the metal salt additive substantially improves the technical effect of rhodium in catalysis of asymmetric hydrogenation and enhances reaction yield and optical purity of the product; and production process is simplified, production cost is lowered, and the preparation method is suitable for industrial large-scale production.
-
Paragraph 0286-0292

(2016/10/08)

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.
-
(2016/10/07)

Chemoenzymatic synthesis of (S)-duloxetine using carbonyl reductase from Rhodosporidium toruloides
A chemoenzymatic strategy was developed for (S)-duloxetine production employing carbonyl reductases from newly isolated Rhodosporidium toruloides into the enantiodetermining step. Amongst the ten most permissive enzymes identified, cloned, and overexpressed in Escherichia coli, RtSCR9 exhibited excellent activity and enantioselectivity. Using co-expressed E. coli harboring both RtSCR9 and glucose dehydrogenase, (S)-3-(dimethylamino)-1-(2-thienyl)-1-propanol 3a was fabricated with so far the highest substrate loading (1000 mM) in a space-time yield per gram of biomass (DCW) of 22.9 mmol L-1 h-1 g DCW-1 at a 200-g scale. The subsequent synthetic steps from RtSCR9-catalyzed (S)-3a were further performed, affording (S)-duloxetine with 60.2% overall yield from 2-acethylthiophene in >98.5% ee.
Chen, Xiang,Liu, Zhi-Qiang,Lin, Chao-Ping,Zheng, Yu-Guo
p. 82 - 89
(2016/02/23)

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.
-
Paragraph 0030-0031

(2017/03/08)

A method for preparing optically active 3-amino-1-propanol derivatives as an intermediate and a method for preparing (S)-duloxetine using the same
The present invention relates to a method for preparing optically active 3-AMNO1-propanol derivatives as an intermediate and a method for preparing (s)-duloxetine using the same. This method can obtain optically active 3-AMNO1-propanol with higher yield and optical purity (ee) than any other conventional methods. Using this as an intermediate compound, it is possible to manufacture duloxetine which is enantiomerically pure and has high optical purity (ee).(DD) Nisoxetine(EE) Duloxetine(CC) 3-amino-1-propanol(BB) Fluoxetine(AA) TomoxetineCOPYRIGHT KIPO 2015
-
Paragraph 0216-0218

(2016/12/01)

A practical synthesis of the antidepressant (S)-duloxetine
-
Lee, Sun-Ah,Sadu, Venkata Subbaiah,Park, No-Joong,Hwang, In-Taek,Lee, Kee-In
p. 1894 - 1896
(2014/07/07)

Copper(ii)-catalyzed enantioselective hydrosilylation of halo-substituted alkyl aryl and heteroaryl ketones: Asymmetric synthesis of (R)-fluoxetine and (S)-duloxetine
A set of reaction conditions has been established to facilitate the non-precious copper-catalyzed enantioselective hydrosilylation of a number of structurally diverse β-, γ- or ε-halo-substituted alkyl aryl ketones and α-, β- or γ-halo-substituted alkyl heteroaryl ketones under air to afford a broad spectrum of halo alcohols in high yields and good to excellent enantioselectivities (up to 99% ee). The developed procedure has been successfully applied to the asymmetric synthesis of antidepressant drugs (R)-fluoxetine and (S)-duloxetine, which highlighted its synthetic utility.
Zhou, Ji-Ning,Fang, Qiang,Hu, Yi-Hu,Yang, Li-Yao,Wu, Fei-Fei,Xie, Lin-Jie,Wu, Jing,Li, Shijun
p. 1009 - 1017
(2014/02/14)

Total synthesis of fluoxetine and duloxetine through an in situ imine formation/borylation/transimination and reduction approach
We report efficient, catalytic, asymmetric total syntheses of both (R)-fluoxetine and (S)-duloxetine from α,β-unsaturated aldehydes conducting five sequential one-pot steps (imine formation/copper mediated β-borylation/transimination/reduction/oxidation) followed by the specific ether group formation which deliver the desired products (R)-fluoxetine in 45% yield (96% ee) and (S)-duloxetine in 47% yield (94% ee). This journal is the Partner Organisations 2014.
Calow, Adam D. J.,Fernandez, Elena,Whiting, Andrew
p. 6121 - 6127
(2014/08/05)

Concise enantioselective synthesis of duloxetine via direct catalytic asymmetric aldol reaction of thioamide
Direct catalytic asymmetric aldol reaction of thioamide offers a new entry to the concise enantioselective synthesis of duloxetine. The direct aldol protocol was scalable (>20 g) to afford the aldol product in 92% ee after LiAlH4 reduction, and 84% of the chiral ligand was recovered after recrystallization. The following four steps of transformation delivered duloxetine.
Suzuki, Yuta,Iwata, Mitsutaka,Yazaki, Ryo,Kumagai, Naoya,Shibasaki, Masakatsu
experimental part
p. 4496 - 4500
(2012/06/30)

"Process for the preparation of duloxetine and its hydrochloride salt"
A process for the preparation of duloxetine (N-methyl-3-(1-naphthyloxy)-3-(thiophen-2-yl)-propanamine) of formula IV: and its hydrochloride salt, comprising the following steps: Compound (II) is reacted with an alkali metal hydride in sulfolane to (III). Crude (III) is purified by a double extraction process; Purified (III) is then demethylated to give (IV). The process is characterized by being safer, allowing solvent recovery limiting the racemization of the key intermediates.
-
Page/Page column 8

(2012/10/18)

PHARMACEUTICAL COMPOSITION OF DULOXETINE OR PHARMACEUTICALLY
The invention relates to a taste masked pharmaceutical composition comprising duloxetine or pharmaceutically acceptable salts thereof. The invention also relates to processes for the preparation of such compositions. The invention further discloses an inclusion complex comprising duloxetine or pharmaceutically acceptable salts thereof with one or more cyclodextrin or derivatives thereof.
-
(2012/07/13)

PROCESS FOR PREPARING (S)-(+)-N-METHYL-3-(1-NAPHTHYLOXY)-3-(2-THIENYL)PROPYLAMINE BY USING OPTICALLY ACTIVE METHYLHYDROXYLAMINOPROPANOL COMPOUND AS INTERMEDIATE
The present invention provides (S)-methylhydroxylaminopropanol compound as an intermediate in preparation of (S)-(+)-N-methyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine. The present invention also provides a process for preparing (S)-(+)-N-methyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine with higher yield and lower cost by using the (S)-methylhydroxylaminopropanol compound as an intermediate.
-
Page/Page column 4

(2011/11/13)

Process for preparing (S)-(+)-N-methyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine by using an optically active methylhydroxylaminopropanol compound as intermediate
The present invention provides (S)-methylhydroxylaminopropanol compound as an intermediate in preparation of (S)-(+)-N-methyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine. The present invention also provides a process for preparing (S)-(+)-N-methyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine with higher yield and lower cost by using the (S)-methylhydroxylaminopropanol compound as an intermediate.
-
Page/Page column 6-7

(2011/12/01)

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).
-
(2011/07/09)

A facile asymmetric synthesis of (S)-duloxetine
The asymmetric-transfer hydrogenation of 2-tosyloxy-1-(2-thiophenyl) ethanone and further elaboration of the cyclic carbamate derived from ?-aminoalcohol to provide a facile synthesis of (S)-duloxetine, a potent dual inhibitor of serotonin and norepinephrine reuptake, is described. ARKAT USA, Inc.
Kwak, Se Hun,Seo, Jung Min,Leea, Kee-In
experimental part
p. 55 - 61
(2011/01/12)

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.
-
Page/Page column 23-24

(2010/04/03)

PREPARATION OF (S)-(+)-N-METHYL-3-(1-NAPHTHYLOXY)-3-(2-THIENYL) PROPYLAMINE USING OPTICALLY ACTIVE METHYLHYDROXYLAMINOPROPANOL DERIVATIVE AS AN INTERMEDIATE
The present invention provides a (S)-methylhydroxylaminopropanol derivative as an intermediate for preparation of (S)-(+)-N-methyl-3-methyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine. The present invention also provides a process for preparing (S)-(+)-N-methyl-3-methyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine with higher yield and lower cost, wherein the (S)-methylhydroxylaminopropanol derivative is used as an intermediate.
-
Page/Page column 4

(2010/09/18)

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.
-
Page/Page column 26-27

(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.
-
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.
-
Page/Page column 3-4

(2010/11/03)

PROCESS FOR THE PREPARATION ENANTIOMERICALLY PURE SALTS OF N-METHYL-3-(1-NAPHTHALENEOXY)-3-(2-THIENYL)PROPANAMINE
The present invention relates to duloxetine salts having enantiomeric purity of 98% or more and a process for such salts.
-
Page/Page column 3

(2010/12/29)

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

(2010/11/03)

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

(2010/10/03)

SYNTHESIS AND PREPARATIONS OF DULOXETINE SALTS
The invention relates to an improved process for the preparation of duloxetine hydrochloride.
-
Page/Page column 4

(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%.
-
Page/Page column 21

(2009/04/25)

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.
-
Page/Page column 17-18

(2009/10/22)

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.
-
Page/Page column 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.
-
Page/Page column 3

(2009/12/02)

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.
-
Page/Page column 8

(2009/06/27)

PAINKILLING ASSOCIATION COMPRISING A DIHYDROIMIDAZOPYRAZINE DERIVATIVE
The invention relates to a product comprising (1R)-1-[(({2R)-2-amino-3-[(8S)-8-(cyclohexylmethyl) -2-phenyl-5,6-dihydroimidazo [1,2-a]pyrazin-7(8H)-yl]-3-oxopropyl}dithio)methyl]-2-[(8S)-8-(cyclohexylmethyl) -2-phenyl-5,6-dihydrolmidazo[1,2-a]pyrazin-7(8H)-yl]-2-oxoethylamine in association with an analgesic agent selected from morphine, the similar or a morphine derivative, sodium channel inhibitors, non-steroidal antiflammatory agents (AINS), glutamatergic system inhibitors, tricycle antidepressants and gabaergic derivatives for simultaneous therapeutic use which is separated or out over the time for pain treatment or prevention.
-
(2009/10/31)

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.
-
Page/Page column 3

(2008/12/09)

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.
-
Page/Page column 16-17

(2008/12/07)

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).
-
Page/Page column 23; 24-25

(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).
-
Page/Page column 36

(2008/12/07)

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.
-
Page/Page column 22

(2008/12/06)

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.
-
Page/Page column 7

(2008/12/06)

PROCESS FOR THE PREPARATION OF DULOXETINE AND ITS SALTS
The present invention relates to duloxetine salts having enantiomeric purity of 98% or more and a process for such salts.
-
Page/Page column 8

(2008/06/13)

IMPROVED PROCESS FOR THE ASYMMETRIC SYNTHESIS OF DULOXETINE
This invention provides an improved asymmetric process for the synthesis of duloxetine involving arylation of Compounds of Formula I.
-
Page/Page column 3; 4

(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).
-
Page/Page column 9; 10

(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.
-
Page/Page column 5

(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.
-
Page/Page column 18

(2008/06/13)

DNT-benzenesulfonate and methods of preparation thereof
(S)—N,N-Dimethyl-3-(1-naphthalenyloxy)-3-(2-thienyl)propanamine benzenesulfonate (DNT-benzenesulfonate) and polymorphs of DNT-benzenesulfonate, compositions of DNT-benzenesulfonate and its polymorphs, processes for the preparation of DNT-benzenesulfonate and its polymorphs, and processes for the preparation of duloxetine hydrochloride from DNT-benzenesulfonate are provided.
-
Page/Page column 4

(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.
-
Page/Page column 15-16

(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.
-
Page/Page column 19-20

(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.
-
Page/Page column 6-7

(2010/11/28)

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.
-
Page/Page column 10

(2010/11/28)

Process for preparing duloxetine and intermediates thereof
Processes for preparing chemically pure duloxetine and chemically pure duloxetine intermediates are provided.
-
Page/Page column 5-6

(2010/11/29)