- METHOD FOR THE PREPARATION OF TAPENTADOL AND ITS INTERMEDIATES
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A method for the preparation of tapentadol in the form of a base or its hydrogen chloride, which involves the preparation of a salt (III) from a mixture of diastereomers (II) by means of crystallization-induced asymmetric transformation (CIAT) through oxo
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- A synthetic hydrochloric acid he spurts he number of method
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The invention discloses a method for synthesizing tapentadol hydrochloride. The method comprises a reaction route shown in the specification. In the reaction route, R1 is one of halogens, -OH, -OR4, -NO2, -NH2, -NR5R6, -SH and -SR7. A required chiral isomer is directly obtained through a reaction under chiral catalysis, so the method has the advantages of avoiding of problems of a large amount of wastes and environmental protection due to chiral splitting, short route, simple operation, easy industrialization, high raw material utilization rate, great improvement of the yield, cost reduction, meeting of requirements of industrial production of tapentadol hydrochloride, and significant progress.
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Paragraph 0112; 0113
(2017/08/25)
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- NEW SYNTHESIS OF TAPENTADOL-HCl INTERMEDIATES
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The present invention relates to a process for the synthesis of tapentadol intermediates comprising the following route of synthesis: (I) → (II) → (III) → (IV) → (V).
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Page/Page column 19
(2017/01/02)
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- A he spurts him number of synthetic method
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The invention discloses a synthetic method of tapentadol. The method comprises the following steps: reacting meta-substitution cinnamic acid serving as a starting material with a chiral adjuvant to obtain amide; reacting the amide with a nucleophilic reagent and an electrophilic reagent, and introducing two chiral centers to obtain a chiral product; performing reduction and deprotection on the chiral product to obtain chiral alcohol; performing an amination reaction and a substitution reaction on the chiral alcohol to obtain the tapentadol. The tapentadol is synthesized by taking cheap and readily-available (1R,2R)-psedo-ephedrine as the chiral adjuvant, forming two chiral centers by using a one-pot method and performing simper deprotection and subsequent transformation. By adopting the synthetic method, the reaction route can be simplified, post-treatment steps can be reduced, and the production cost is reduced. The synthetic method is more suitable for industrial application.
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- Novel Intermediate Used for Preparing Tapentadol or Analogues Thereof
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The invention discloses a novel intermediate for preparing tapentadol and analogues thereof, wherein the structural formula is shown as formula I or II, and the groups are defined as the specification. The invention further discloses a method for preparing the novel intermediate and use of the intermediate for preparing tapentadol and analogues thereof. The invention can remarkably improve the product yield and quality of tapentadol, reduce the production cost, and simplify the production procedure. The preparation process is environment friendly, thus more suitable for the requirements of industrial production.
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- STABLE POLYMORPH FORM B OF TAPENTADOL HYDROCHLORIDE
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The present invention relates to Tapentadol Hydrochloride in the polymorphic crystalline Form B, which is substantially free of polymorphic Form A as well as essentially free of low alkyl carboxylic acids or esters of such acids. Furthermore, the present
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Page/Page column 20
(2015/09/22)
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- A NOVEL PROCESS FOR THE PREPARATION OF 1-PHENYL-3-AMINOPROPANE DERIVATIVES
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The present invention relates to a novel process for the preparation of 1-phenyl-3- aminopropane derivative compounds corresponding to the formula (I) and/or its intermediates, and/or its stereo specific isomers or pharmaceutically acceptable salts, hydra
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Page/Page column 25
(2015/06/08)
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- NOVEL INTERMEDIATE OF TAPENTADOL
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The present invention relates to novel carbamate intermediate of formula (II), process for its preparation and process for its conversion into 3-[(1R,2R)-3-(dimethylamino)-1-ethyl-2-methylpropyl]phenol, tapentadol and its pharmaceutically acceptable salts
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Page/Page column 17
(2015/06/08)
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- Substituted n-pentanamide compounds, preparation method and the use thereof
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The present invention relates to a (2R, 3R)-3-(3-substituted phenyl)-2-methyl n-pentanamide compounds as shown in the formula I and the preparation method thereof, wherein, the substituents are as defined in the specification, the present invention further relates to a use of the above compounds for the preparation of tapentadol II or its pharmaceutically acceptable salt, and the intermediates involved in the preparation process.
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- TAPENTADOL MALEATE AND CRYSTALLINE FORMS THEREOF
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Disclosed herein is a novel and stable salt of tapentadol, tapentadol maleate, its polymorphic Forms as well as processes for its preparation, pharmaceutical compositions, and preparation thereof.
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- Compounds and Methods for Preparing Substituted 3-(1-amino-2-methylpentane-3-yl)phenyl Compounds
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Compounds and methods for preparing substituted 3-(1-amino-2-methylpentane-3-yl)phenyl compounds from an isomerically pure starting material are described. In particular, methods of preparing a 3-(1-(dimethylamino)-2-methylpentane-3-yl)phenol as a substan
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Paragraph 0148
(2014/12/09)
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- PROCESS FOR PREPARING L-PHENYL-3-DIMETHYLAMINOPROPANE DERIVATIVE
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Provided is a process for the preparing 1-phenyl-3-dimethylaminopropane derivatives of formula I, (The formula should be inserted here) and its pharmaceutically acceptable salts thereof via novel intermediates.
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- SUBSTITUTED N-PENTANAMIDE COMPOUNDS, PREPARATION METHODS AND USES THEREOF
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The present invention relates to a (2R, 3R)-3-(3-substituted phenyl)-2-methyl n-pentanamide compounds as shown in the formula I and the preparation method thereof, wherein, the substituents are as defined in the specification, the present invention further relates to a use of the above compounds for the preparation of tapentadol II or its pharmaceutically acceptable salt, and the intermediates involved in the preparation process.
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- STEREOSELECTIVE SYNTHESIS OF TAPENTADOL AND ITS SALTS
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A process for the synthesis of a salt of tapentadol.
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- PROCESS FOR THE SYNTHESIS OF TAPENTADOL AND INTERMEDIATES THEREOF
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The object of the present invention is a new process for the synthesis of tapentadol, both as free base and in hydrochloride form, which comprises the step of alkylation of the ketone (VII) to yield the compound (VIII), as reported in Diagram 1, with high
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Paragraph 0107; 0108
(2013/07/19)
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- PROCESS FOR THE PREPARATION OF TAPENTADOL
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Disclosed herein is an improved process for the preparation of 3-[(2R,3R)-1-(dimethylamino)-2-methylpentan-3-yl]phenol of Formula-I and its pharmaceutically acceptable salt which comprises the reaction of (S)-1-(dimethylamino)-2-methylpentan-3-one of formula VIII with 3-bromo anisole of formula II under Grignard conditions to get the compound (2S, 3R)-1-(dimethylamino)-3-(3-methoxyphenyl)-2-methyl pentan-3-ol of formula V followed by activation of the —OH group of the formula V to convert into sulfonate esters of formula IX, which are on reductive deoxygenation to yield (2R,3R)-3-(3-methoxyphenyl)-N,N,2-trimethylpentan-1-amine of formula VII and demethylation of formula VII to obtain the compound 3-[(2R,3R)-1-(dimethylamino)-2-methylpentan-3-yl]phenol of Formula-1.
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Paragraph 0063; 0064; 0065
(2013/06/05)
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- PROCESS FOR THE PREPARATION OF TAPENTADOL
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Disclosed herein is a process for the preparation of the compound 3-[(2R,3R)-1-(dimethylamino)-2-methylpentan-3-yl]phenol comprising a) reacting compound (2S,3R)-1-(dimethylamino)-3-(3-methoxyphenyl)-2-methylpentan-3-ol with a mixture of methanesulfonic a
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Page/Page column 15; 16
(2013/07/25)
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- NOVEL INTERMEDIATE USED FOR PREPARING TAPENTADOL OR ANALOGUES THEREOF
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The invention discloses a novel intermediate for preparing tapentadol and analogues thereof, wherein the structural formula is shown as formula I or II, and the groups are defined as the specification. The invention further discloses a method for preparing the novel intermediate and use of the intermediate for preparing tapentadol and analogues thereof. The invention can remarkably improve the product yield and quality of tapentadol, reduce the production cost, and simplify the production procedure. The preparation process is environment friendly, thus more suitable for the requirements of industrial production.
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- NOVEL PROCESS FOR PREPARING HIGHLY PURE TAPENTADOL OR A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF
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Provided herein is a novel, commercially viable and industrially advantageous process for the preparation of 3-[(1R,2R)-3-(dimethylamino)-1-ethyl-2-methylpropyl]phenol (Tapentadol), or a pharmaceutically acceptable salt thereof, and its intermediates, in high yield and purity. Provided also herein are novel solid state forms of tapentadol intermediates and processes for their preparation thereof. Provided further herein is a purification process for preparing highly pure tapentadol hydrochloride.
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Paragraph 0164; 0165
(2013/04/24)
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- PROCESS FOR PREPARING L-PHENYL-3-DIMETHYLAMINOPROPANE DERIVATIVE
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Provided is a process for the preparing l-phenyl-3-dimethylaminopropane derivatives of formula I, (The formula should be inserted here) and its pharmaceutically acceptable salts thereof via novel intermediates.
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- A practical and enantioselective synthesis of tapentadol
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A practical and enantioselective synthetic method for tapentadol has been described. Starting from inexpensive and readily available (E)-3-(3-(benzyloxy) phenyl)acrylic acid, tapentadol was prepared in seven steps (44% overall yield and 99.9% de) in more than 100 g batches, without any chromatographic purification. An Evans' chiral auxiliary based conjugate addition and alkylation were used as the key steps.
- Zhang, Qiang,Li, Jian-Feng,Tian, Guang-Hui,Zhang, Rong-Xia,Sun, Jin,Suo, Jin,Feng, Xin,Fang, Du,Jiang, Xiang-Rui,Shen, Jing-Shan
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p. 577 - 582
(2012/08/27)
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- NEW PROCESS FOR THE SYNTHESIS OF TAPENTADOL AND INTERMEDIATES THEREOF
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The object of the present invention is a new process for the synthesis of tapentadol, both as free base and in hydrochloride form, which comprises the step of alkylation of the ketone (VII) to yield the compound (VIII), as reported in Diagram 1, with high
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Page/Page column 18
(2012/01/14)
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- PROCESS FOR THE PREPARATION OF TAPENTADOL
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Disclosed herein is an improved process for the preparation of 3-[(2R,3R)-1- (dimethylamino)-2-methylpentan-3-yl] phenol of Formula - I and its pharmaceutically acceptable salt which comprises the reaction of (S)-1-(dimethylamino)-2-methylpentan- 3-one of formula VIII with 3 - bromo anisole of formula II under Grignard conditions to get the compound (2S, 3R)-1- (dimethylamino)-3-(3-methoxyphenyl)-2-methyl pentan-3- ol of formula V followed by activation of the -OH group of the formula V to convert into sulfonate esters of formula IX, which are on reductive deoxygenation to yield (2R,3R)-3- (3-methoxyphenyl)-N,N,2-trimethylpentan-1 -amine of formula VII and demethylation of formula VII to obtain the compound 3-[(2R,3R)-1-(dimethylamino)-2-methylpentan-3- yl]phenol of Formula - 1.
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Page/Page column 17
(2012/03/11)
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- TAPENTADOL HYDROBROMIDE AND CRYSTALLINE FORMS THEREOF
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The present invention provides a salt of Tapentadol, Tapentadol liydrobromide, and crystalline forms of Tapentadol hydrobromide.
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Page/Page column 7
(2012/05/04)
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- A NOVEL PROCESS FOR THE PREPARATION OF TAPENTADOL OR A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF
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Disclosed herein is a novel, commercially viable and industrially advantageous process for the preparation of 3-[(1R,2R))-3-(dimethylamino)-1-ethyl-2-methylpropyl]phenol (Tapentadol), or a pharmaceutically acceptable salt thereof, in high yield and purity. Also described are novel intermediates useful for preparing tapentadol or a pharmaceutically acceptable salt thereof.
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Page/Page column 23-24
(2012/11/13)
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- O-SUBSTITUTED (2R,3R)-3-(3-HYDROXYPHENYL)-2-METHYL-4-PENTENOIC ACIDS AND A METHOD OF OBTAINING THE SAME
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The compounds of general formula II are new and represent important intermediates in the synthesis of tapentadol. In the synthesis of tapentadol of formula I and its pharmaceutically acceptable salts, O-protected (2R,3R)-acids of general formula II, in step A, are reacted in an inert organic solvent with an activating agent, optionally in presence of a catalyst or a base; in step B, the obtained compounds of general formula V, wherein R has the above mentioned meaning and X stands for chlorine or alkoxycarbonyloxyl group O-CO-OR1 or pivaloyloxyl O-CO-t-Bu group, wherein R1 is methyl or ethyl, are reacted with dimethylamine or its salts optionally in presence of a base; in step C, the obtained N, N-dimethylamides of general formula VI, wherein R has the above mentioned meaning, are reduced by means of hydride agents in a suitable solvent; in step D, the produced alkeneamines of general formula VII, wherein R has the above mentioned meaning, are hydrogenated on a metal catalysts in a suitable solvent; and, finally, in step E, the produced alkaneamines of general formula VIII, wherein R has the above mentioned meaning, are O-dealkylated by means of dealkylating agents, and, if required, the obtained tapentadol is converted by the action of a pharmaceutically acceptable acid to respective salts, e.g. hydrochloride.
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- Process for Preparing Substituted 3-(1-amino-2-methylpentane-3-yl)phenyl Compounds
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A process for the preparation of substituted 3-(1-amino-2-methylpentane-3-yl)phenyl compounds.
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Page/Page column 18
(2012/01/03)
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- PROCESS FOR THE PREPARATION OF 1-PHENYL-3-DIMETHYLAMINOPROPANE DERIVATIVES
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A process for the preparation of 1-phenyl-3-dimethylaminopropane derivatives of formula (I) and its pharmaceutically acceptable salts thereof from cyano intermediate of formula (II), wherein R1 can be selected from -OR2, halo, -CH2OR2, -SR2, -SOR2, SO2R2, -SO3H, -NO2, -NR2R2', -CONR2R2', carboxylic esters, sulfonate esters or phosphate esters, R2 and R2' can be same or different, and can be selected from hydrogen, alkyl, aryl, aralkyl, heteroaryl, -COR2", -P03(R2")2 wherein R2" can be selected from alkyl, aryl, aralkyl, heteroaryl and the like.
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Page/Page column 46
(2011/07/30)
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- Four stereoisomers of the novel -opioid receptor agonist tapenta-dol hydro-chloride
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The crystal and mol-ecular structures of four stereoisomers of tapenta-dol hydro-chloride [systematic name: 3-(3-hy-droxy-phenyl)-N,N,2-trimethyl-pentan-1- aminium chloride], C14H24NO+·Cl -, a novel analgesic ag
- Ravikumar, Krishnan,Sridhar, Balasubramanian,Pradhan, Nitin,Khunt, Mayur
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experimental part
p. o71-o76
(2011/05/07)
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- PROCESS FOR THE PREPARATION OF L-PHENYL-3-DIMETHYLAMINOPROPANE DERIVATIVES
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The present invention provides a process for the preparation of 1-phenyl-3-dimethylaminopropane derivatives of formula I, and its pharmaceutically acceptable salts thereof from intermediate of formula II, wherein R1 can be selected from -OR2, halo, -CH2OR2, -SR2, SOR2, SO2R2, -SO3H, -NO2, -NR2R2', - CONR2R2 ', carboxylic esters, sulfonate esters or phosphate esters and the like; R ' can be selected from hydrogen, alkyl, aryl, aralkyl, alkaryl, heteroaryl, and the like; or OR ' can be selected from -NR2R2 '; or R2 and R2 ' can be same or different and can be selected from hydrogen, alkyl, aryl, aralkyl, heteroaryl,-OR3, - COR3, -PO3(R3R4) wherein R3 and R4 can be same or different and can be selected from alkyl, aryl, aralkyl, heteroaryl and the like.
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- PRODRUGS OF OPIOIDS AND USES THEREOF
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The present invention concerns prodrugs of opioid analgesics and pharmaceutical compositions containing such prodrugs. Methods for providing more consistent pain relief by increasing the bioavailability of the opioid analgesic with the aforementioned prodrugs are provided. The invention also provides for decreasing the adverse GI side effects of opioid analgesics.
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Page/Page column 68-69
(2011/08/08)
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- SOLID STATE FORMS OF TAPENTADOL SALTS
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Provided herein are novel solid state forms of tapentadol salts, process for their preparation, pharmaceutical compositions, and method of treating thereof. The tapentadol salts include an L-(?)-camphorsulfonate salt, a dibenzoyl-(L)-tartrate salt, a dibe
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Page/Page column 6-7
(2011/04/18)
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- PROCESS FOR THE PREPARATION OF SUBSTITUTED 3-(1-AMINO-2-METHYLPENTANE-3-YL)PHENYL COMPOUNDS
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The present invention relates to a process for the preparation of substituted 3-(1-amino-2-methylpentane-3-yl)phenyl compounds.
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- INTERMEDIATE COMPOUNDS AND PROCESSES FOR THE PREPARATION OF TAPENTADOL AND RELATED COMPOUNDS
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The present invention discloses processes for the preparation of 3-[(1R,2R)-3-(dimethyl- amino)-1-ethyl-2-methylpropyl]phenol (Tapentadol), salts thereof and related compounds of formula (A), including stereoisomers and pharmaceutically acceptable salts t
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Page/Page column 51
(2011/07/30)
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- IMPROVED RESOLUTION METHODS FOR ISOLATING DESIRED ENANTIOMERS OF TAPENTADOL INTERMEDIATES AND USE THEREOF FOR THE PREPARATION OF TAPENTADOL
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Provided herein is an improved and industrially advantageous optical resolution method for resolving (2R,3R)/(2S,3S)-l-dimethylamino-3-(3-methoxyphenyl)-2- methylpentan-3-ol, and use thereof for the preparation of tapentadol or a pharmaceutically acceptable salt thereof. Provided further herein is an improved and industrially advantageous optical resolution method for resolving (2R,3R)/(2S,3S)-[3-(3-methoxyphenyl)-2- methylpentyl]-dimethylamine, and use thereof for the preparation of tapentadol or a pharmaceutically acceptable salt thereof. Disclosed also herein is an improved, commercially viable and industrially advantageous process for the preparation of tapentadol or a pharmaceutically acceptable salt thereof in high yield and purity.
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- NEW PROCESS FOR THE PREPARATION OF TAPENTADOL AND INTERMEDIATES THEREOF
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The present invention refers to a new process for the synthesis of tapentadol comprising the quantitative resolution of the racemic mixture (V) to obtain the stereoisomer of (S)-3-(dimethylamino)-2-methyl-l-(3-nitrophenyl)-propan-l-one (VII) according to
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- AMINO ACID AND PEPTIDE CARBAMATE PRODRUGS OF TAPENTADOL AND USES THEREOF
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Prodrugs of tapentadol with amino acids or short peptides, pharmaceutical compositions containing such prodrugs and a method for providing pain relief with the tapentadol prodrugs are provided herein. Prodrugs having side chains of valine, leucine, isoleucine and glycine amino acids and mono-, di- and tripeptides thereof are preferred. Additionally, methods for avoiding or minimizing the adverse gastrointestinal side effects associated with tapentadol administration, as well as increasing the oral bioavailability of tapentadol are provided herein.
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Page/Page column 10
(2010/09/17)
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- PROCESS FOR THE PREPARATION OF (1R,2R)-3-(3-DIMETHYLAMINO-1-ETHYL-2-METHYL-PROPYL)-PHENOL
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The present invention relates to a process for the preparation of (1 R,2R)-3- dimethylamino-1-ethyl-2-methyl-propyl)-phenol.
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Page/Page column 23
(2008/06/13)
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- PREPARATION OF 3-[(1R,2R)-3-(DIMETHYLAMINO)-1ETHYL-2-METHYLPROPYL]PHENOL
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The present invention relates to an improved process for the preparation of 3- [(1R,2R)-3-(dimethylamino)-1-ethyl-2-methylpropyl]phenol monohydrochloride.
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Page/Page column 11-12
(2008/06/13)
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- 1-phenyl-3-dimethylaminopropane compounds with a pharmacological effect
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1-phenyl-3-dimethylaminopropane compounds corresponding to the formula I a method of preparing them, and the use of these substances as analgesic active ingredients in pharmaceutical compositions.
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- 1-phenyl-3-dimethylaminopropane compounds with a pharmacological effects
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1-phenyl-3 -dimethylaminopropane compounds corresponding to the formula I a method of preparing them, and the use of these substances as analgesic active ingredients in pharmaceutical compositions.
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