- Synthesis method of dapoxetine
-
The present invention provides a synthesis method of dapoxetine, comprising the following steps: S1, the (s)-3-amino-3-phenylpropionic acid or ester compounds dispersed in a solvent, reflux reaction under the action of a reducing agent, to give (s) - amino-3-phenylpropanol; S2, the (s) - amino-3-phenylpropanol dissolved in aqueous solution of carboxylic acid, added paraformaldehyde to warm up the reaction, to give (s) -3-dimethylamino-3-phenylpropanol; S3, (s)-3-Dimethylamino-3-phenylpropanol was dissolved in a solvent, protected by nitrogen, and reacted in a solution of alkali added dropwise at a higher temperature, and then 1-fluoronaphthalene was added to produce Williamson etherization reaction, to give (s)-N, N-dimethyl-3-(1-naphthooxy) amphetamine, i.e., dapoxetine. The synthesis method of dapoxetine of the present invention is inexpensive and easy to obtain raw materials, does not use toxic and dangerous reagents, will not react to the phenomenon of aggregation spray, the process is simple, suitable for industrial production.
- -
-
Paragraph 0040; 0045-0046; 0051; 0055-0056; 0061
(2022/01/12)
-
- Enantioconvergent Cu-Catalyzed Radical C-N Coupling of Racemic Secondary Alkyl Halides to Access α-Chiral Primary Amines
-
α-Chiral alkyl primary amines are virtually universal synthetic precursors for all other α-chiral N-containing compounds ubiquitous in biological, pharmaceutical, and material sciences. The enantioselective amination of common alkyl halides with ammonia is appealing for potential rapid access to α-chiral primary amines, but has hitherto remained rare due to the multifaceted difficulties in using ammonia and the underdeveloped C(sp3)-N coupling. Here we demonstrate sulfoximines as excellent ammonia surrogates for enantioconvergent radical C-N coupling with diverse racemic secondary alkyl halides (>60 examples) by copper catalysis under mild thermal conditions. The reaction efficiently provides highly enantioenrichedN-alkyl sulfoximines (up to 99% yield and >99% ee) featuring secondary benzyl, propargyl, α-carbonyl alkyl, and α-cyano alkyl stereocenters. In addition, we have converted the masked α-chiral primary amines thus obtained to various synthetic building blocks, ligands, and drugs possessing α-chiral N-functionalities, such as carbamate, carboxylamide, secondary and tertiary amine, and oxazoline, with commonly seen α-substitution patterns. These results shine light on the potential of enantioconvergent radical cross-coupling as a general chiral carbon-heteroatom formation strategy.
- Cheng, Jiang-Tao,Dong, Xiao-Yang,Gu, Qiang-Shuai,Li, Zhong-Liang,Liu, Juan,Liu, Xin-Yuan,Luan, Cheng,Wang, Fu-Li,Wang, Li-Lei,Yang, Ning-Yuan,Zhang, Yu-Feng
-
supporting information
p. 15413 - 15419
(2021/09/30)
-
- Preparation and detection method of dapoxetine hydrochloride isomer impurities
-
The invention discloses a preparation process for preparing a dapoxetine hydrochloride beta-isomer impurity shown as formula I and an enantiomer shown as formula II. The method comprises the following steps: taking optically pure Boc-(S) or (R)-3-amino-3-phenylpropanol as a raw material, performing condensation reaction with 2-fluoronaphthalene or 1-fluoronaphthalene, performing methylation reaction with formic acid-formaldehyde, and performing HCl salification reaction to obtain a target product dapoxetine hydrochloride beta-isomer or enantiomer impurity. Meanwhile, a detection method of isomer impurities is developed.
- -
-
Paragraph 0013; 0017; 0019-0020
(2020/05/01)
-
- Related substances of dapoxetine hydrochloride, preparation method and applications thereof
-
The invention relates to related substances of dapoxetine hydrochloride, a preparation method and applications thereof, wherein the related substances are (R)-3-((R)-3-(naphthalene-1-oxy)-1-phenylpropoxy)-1-phenylpropyl-1-ol and/or (S)-N,N-dimethyl-3-((R)-3-(naphthalene-1-oxy)-1-phenylpropoxy)-1-phenylpropyl-1-amine and a salt thereof, especially a hydrochloride. According to the invention, by detecting and controlling the related substances provided by the invention in the production and quality inspection of dapoxetine hydrochloride, an intermediate, a bulk drug and a preparations thereof, the drug quality of dapoxetine hydrochloride is further improved, possible side effects are reduced, and the medication safety is improved.
- -
-
-
- Preparation method of dapoxetine hydrochloride racemate
-
The invention discloses a preparation method of a dapoxetine hydrochloride racemate, which comprises the following steps: by using 1-(3-phenylpropoxy) naphthalene as a raw material, carrying out halogenation, amination, hydrogenation dehalogenation and the like to obtain a dapoxetine hydrochloride racemate (V); the method disclosed by the invention is high in yield, convenient in post-treatment and more suitable for industrial production.
- -
-
-
- Synthetic method of dapoxetine and intermediate thereof
-
The invention discloses a synthetic method of dapoxetine and its intermediate, i.e., (S)-3-(tert-butyloxycarbonyl)amino-3-phenylpropanol as shown in a formula 5 which is described in the specification. The synthetic method of (S)-3-(tert-butyloxycarbonyl)amino-3-phenylpropanol is as shown in a synthesis route which is described in the specification, wherein a compound 3 and acetaldehyde are subjected to a Mannich reaction in an organic solvent under the action of a supramolecular catalyst constructed by a chiral catalyst and a polymer so as to obtain a compound 4, and the polymer is at least one selected from of the group consisting of PEG 200, PEG 400, PEG 600, MeOPEG 750, PEG 800, PEG 1000, PPG 800 and PPG 1000. The dapoxetine is synthesized from the (S)-3-(tert-butyloxycarbonyl)amino-3-phenylpropanol prepared by using the above method according to steps as shown in the synthesis route. The synthetic method of dapoxetine and the intermediate thereof has the characteristics of usage of cheap and easily available raw materials, high yield and low cost, and is more beneficial to industrial production.
- -
-
Paragraph 0110-0113
(2020/03/09)
-
- Development of novel triazole based dendrimer supported spiroborate chiral catalysts for the reduction of (: E)-O-benzyl oxime: An enantioselective synthesis of (S)-dapoxetine
-
Novel dendrimer supported spiroborate catalysts 2 and 3 have been synthesized using a click reaction as a key step. The catalytic efficiency of the catalysts have been verified with reduction of (E)-O-benzyl oxime 13 as a model substrate. Catalyst 3 was found to be better than catalyst 2 as the chemical yield and enantiomeric excess were significantly high with the former catalyst. Thus, catalyst 3 has been successfully used in the efficient synthesis of (S)-dapoxetine 14 with 94% ee and 46% overall yield in three steps. These catalysts could be easily recovered from the reaction solution by the solvent precipitation technique and could be reused five times without significant loss of activity and enantioselectivity.
- Anandhan, Ramasamy,Reddy, Mandapati Bhargava,Sasikumar, Murugesan
-
p. 15052 - 15056
(2019/10/08)
-
- Preparation method of dapoxetine hydrochloride free alkali
-
The invention discloses a preparation method of dapoxetine hydrochloride free alkali. Solid dapoxetine hydrochloride free alkali can be prepared successfully with the method, yield is high, mass production is facilitated, and the method has greater signif
- -
-
Page/Page column 5-8
(2019/03/24)
-
- Synthetic method of dapoxetine
-
The invention belongs to the technical field of medicines, in particular to a synthetic method of dapoxetine. The synthetic method comprises the following steps: adding 1-naphthol and 1-phenyl-3-chloropropanol into acetone as a solvent at a temperature of
- -
-
-
- 5-hydroxytryptamine re-absorption inhibitor crystal form and preparation method thereof
-
The invention relates to a dapoxetine hydrochloride crystal form and a preparation method thereof, and belongs to the technical field of drug synthesis. The preparation method comprises: dissolving (S)-3-amino-3-phenylpropionic acid in an appropriate solvent, adding a reducing agent and a Lewis acid, and reducing to obtain (S)-3-amino-3-phenylpropanol; dissolving the (S)-3-amino-3-phenylpropanolin formic acid, and adding formaldehyde to produce (S)-3-dimethylamino-3-phenylpropanol; dissolving the (S)-3-dimethylamino-3-phenylpropanol in an organic solvent, adding an alkali and 1-fluoronaphthalene, carrying out heating stirring for 5-10 h, adding water and an organic solvent, extracting, carrying out spin drying on the organic phase, dissolving with a solvent, adding concentrated hydrochloric acid in a dropwise manner, and carrying out pressure reducing distillation to remove the solvent and the water; and re-crystallizing with a suitable solvent to obtain the dapoxetine hydrochloride.According to the present invention, the Cu-Ka radiation results of the obtained dapoxetine hydrochloride crystal form show that the characteristic peaks represented by 2[theta] angle are positioned at 6.24+/-0.2, 15.03+/-0.2, 18.87+/-0.2, 20.63+/-0.2 and 25.28+/-0.2 in the X-ray powder diffraction pattern.
- -
-
Paragraph 0045-0054
(2019/08/30)
-
- Synthesis, separation-purification, and salt forming method of dapoxetine
-
The invention provides a novel synthesis, gradient separation-purification, and salt forming method of dapoxetine. Easily available and cheap benzaldehyde is taken as the primary raw material of the synthesis route. The whole reaction conditions are mild. The synthesis route is short. No highly toxic or explosive raw material is used. The problem of chiral separation is well solved in the route. During the separation process, the product is purified. Finally, chlorinated hydromethyl tert-butyl ether which does not have any side or toxic effect is used to carry out salt forming. A large amount of labor, material, and time is saved. The production cost is reduced. The synthesis does not need any special equipment. The operation is simple and convenient. The method has a good industrial application prospect.
- -
-
-
- Midbody for preparing dapoxetine and preparation method for dapoxetine
-
The invention relates to a midbody for preparing dapoxetine and a preparation method for dapoxetine. The dapoxetine hydrochloride with high optical purity can be acquired through a preparation path provided by the invention according to the steps of perfo
- -
-
Paragraph 0034; 0037
(2018/04/02)
-
- A hydrochloric acid west reaches anchors the sandbank preparation method (by machine translation)
-
The invention discloses a method for preparing west reaches anchors the sandbank hydrochloride, including 3 - chlorobenzene propanol, 1 - phenyl - 3 - (1 - naphthoxy) - 1 - propanol, preparation of pure west reaches anchors the sandbank, west reaches anchors the sandbank DTTA salt preparation, preparation of west reaches anchors the sandbank, hydrochloric acid west reaches anchors the sandbank crude preparation and hydrochloric acid west reaches anchors the sandbank preparation of the finished product, the invention, accelerate the speed of production, the saving in material. (by machine translation)
- -
-
-
- Preparation method of dapoxetine hydrochloride
-
The invention discloses a preparation method of dapoxetine hydrochloride. The preparation method comprises that 3-chloropropiophenone and naphthol as initial raw materials and (S)-tert-butanesulfinyl amide undergo a condensation reaction in a solvent, the intermediate is reduced through a reducer BH3 and then is further subjected to deprotection, the reaction product undergoes a methylation reaction and the reaction product undergoes a salification reaction to produce dapoxetine hydrochloride. The preparation method has mild conditions, can be operated simply, realizes a low cost, is free of resolution or use of an expensive heavy metal catalyst, has a simple aftertreatment process, has a high product yield, produces the product with high chemical purity and optical purity and is suitable for industrial production.
- -
-
Paragraph 0020; 0044; 0045
(2017/07/01)
-
- Enantioselective β-hydroxy thioesters formation via decarboxylative aldol reactions of malonic acid half thioesters with aldehydes promoted by chloramphenicol derived sulfonamides
-
A highly enantioselective synthesis of chiral β-hydroxy thioesters that uses a decarboxylative aldol reaction of malonic acid half thioesters and aldehydes catalyzed by a chloramphenicol base-derived bifunctional organocatalyst is reported. The resulting
- Wang, Yafeng,Huang, Guanxin,Hu, Sha,Jin, Kaijun,Wu, Yan,Chen, Fener
-
p. 5055 - 5062
(2017/07/28)
-
- Synthesis technology of N,N-dimethyl-3-(naphthalen-1-yloxy)-1-benzedrine or hydrochloride thereof
-
The invention provides a synthesis technology of N,N-dimethyl-3-(naphthalen-1-yloxy)-1-benzedrine or hydrochloride thereof. According to the synthesis technology, 3-chlorine-1-phenylpropyl-1-ketone and 1-naphthol are taken as starting materials, are condensed in alkaline condition, and then are subjected to amination reduction in methanoic acid solution of dimethylamine, so as to obtain N,N-dimethyl-3-(naphthalen-1-yloxy)-1-benzedrine, and optionally, hydrogen chloride gas is fed into the N,N-dimethyl-3-(naphthalen-1-yloxy)-1-benzedrine, so that the hydrochloride of the N,N-dimethyl-3-(naphthalen-1-yloxy)-1-benzedrine is obtained.
- -
-
Paragraph 0043; 0045; 0048; 0050; 0052; 0054
(2017/08/25)
-
- Chiral Lewis Base-Catalyzed, Enantioselective Reduction of Unprotected β-Enamino Esters with Trichlorosilane
-
Catalytic asymmetric reduction of N-unsubstituted β-enamino esters represents a major challenge for asymmetric catalysis. In this paper, the first organocatalytic system that could be used for the asymmetric hydrosilylation of N-unsubstituted β-enamino esters has been developed. Using N-tert-butylsulfinyl-L-proline-derived amides and L-pipecolinic acid-derived formamides as catalyst, a broad range of β-aryl- and β-alkyl-substituted free β-amino esters could be prepared with high yields and enantioselectivities. The practicality was illustrated by the gram-scale asymmetric synthesis of ethyl (R)-3-amino-3-phenylpropanoate and isopropyl (S)-3-amino-4-(2,3,5-trifluorophenyl)butanoate. The resulting product can be smoothly transformed to the FDA approved medicines dapoxetine and sitagliptin in a short synthetic route.
- Ye, Jianheng,Wang, Chao,Chen, Lin,Wu, Xinjun,Zhou, Li,Sun, Jian
-
supporting information
p. 1042 - 1047
(2016/04/19)
-
- A S - west reaches anchors the sandbank and its salt synthesis method
-
The invention discloses a synthetic method for S-dapoxetine. The synthetic method comprises the following steps: (1) resolving 1-phenyl-3-(naphthyl-1-oxy)propylamine for at least once with a resolving agent to obtain a resolved mixed system; (2) separating the resolved mixed system to obtain S-1-phenyl-3-(naphthyl-1-oxy)propylamine, and recycling mother liquor; (3) performing methylation on the S-1-phenyl-3-(naphthyl-1-oxy)propylamine to obtain S-dapoxetine. Compared with the conventional industrial production method, residual intermediate (R)-phenyl-3-(naphthyl-1-oxy)propylamine in the resolved mother liquor is firstly recycled on the basis of the prior art, then resolved again through D-(-) tartaric acid after racemization, and recycled, so that the yield is increased, the product waste is avoided, and the economic benefits are improved.
- -
-
-
- Chiral preparation method of dapoxetine hydrochloride key intermediate
-
The invention discloses a chiral preparation method of a dapoxetine hydrochloride key intermediate.According to the preparation method, with 3-chloropropiophenone as a raw material and (+)2-ethylmorphine-B-chlorodiisopinocampherylborane Eap2BCl as a reduc
- -
-
-
- A west reaches anchors the sandbank and method for industrial preparation of the intermediates
-
The invention relates to an industrial preparation method of apoxetine and an intermediate of apoxetine. According to the method, methylation, condensation and salt forming reaction are carried out on 3-amino-3-phenyl propanol serving as a starting raw material to obtain the apoxetine and the intermediate of apoxetine. The method overcomes the deficiencies in the prior art, comprises simple and short reaction steps and is convenient and fast to operate and suitable for industrial production; moreover, the raw materials are simple and easily available.
- -
-
-
- Preparation method of dapoxetine and dapoxetine hydrochloride
-
The invention provides a preparation method of dapoxetine. The preparation method comprises the following steps that (S)-(+)-1-phenyl-3-(naphthyl-1-methoxyl) propylamine is freed after a salt forming reaction, and purified (S)-(+)-1-phenyl-3-(naphthyl-1-methoxyl) propylamine is obtained; purified (S)-(+)-1-phenyl-3-(naphthyl-1-methoxyl) propylamine, alkali and formaldehyde are subjected to a tertiary amination reaction in a solvent, and dapoxetine is obtained. Compared with the prior art, the tertiary amination reaction in the preparation method can be completed through only one step, and reaction steps are reduced. It can be known through the experiment result that the product obtained through the preparation method is the target product.
- -
-
Paragraph 0084
(2016/10/10)
-
- Development of Non-C2-symmetric ProPhenol Ligands. the Asymmetric Vinylation of N-Boc Imines
-
The development and application of a new generation of non-C2-symmetric ProPhenol ligands is reported herein. Rational design of the ProPhenol ligand paved the way to the first catalytic and asymmetric vinylation of N-Boc imines via hydrozirconation giving rise to valuable allylic amines in excellent yields and enantioselectivities. The utility of this method was demonstrated by developing the shortest reported asymmetric synthesis of the selective serotonine reuptake inhibitor (SSRI) (-)-dapoxetine.
- Trost, Barry M.,Hung, Chao-I,Koester, Dennis C.,Miller, Yan
-
supporting information
p. 3778 - 3781
(2015/08/18)
-
- A METHOD FOR PREPARING (S)-(+)-N, N-DIMETHYL-3-(NAPHTHALEN-1-YLOXY)-1-PHENYLPROPAN-1-AMINE OR ITS SALT AND INTERMEDIATE THEREOF
-
The present invention is in relation to a method for preparation of (S)-(+)-N, N-dimethyl-[3-(naphthalen-1-yloxy)-1-phenylpropyl]amine or its pharmaceutically acceptable salt and intermediate thereof. The method is industrially viable, economical, eco-fri
- -
-
Page/Page column 11
(2014/03/21)
-
- Process for preparation of enantiomerically pure S-(+)-N, N-dimethyl-a-[2-(naphthalenyloxy)ethyl] benzenemethanamine
-
The present invention relates to improved, efficient process for the preparation of enantiomerically pure S-(+)-N,N-dimethyl-a-[2-(naphthalenyloxy)ethyl] benzenemethanamine and pharmaceutically acid addition salts thereof. The present invention particularly provides a process for preparation of (3S, 4R)-3-hydroxy-1-(4-methoxyphenyl)-4-phenylazetidin-2-one useful as a key intermediate for preparation of (s)-dapoxetine.
- -
-
Paragraph 0106; 0107
(2014/07/09)
-
- Syntheses of a flobufen metabolite and dapoxetine based on enantioselective allylation of aromatic aldehydes
-
The enantioselective allylation of an aromatic aldehyde to give a chiral homoallylic alcohol was employed as the key step in the syntheses of a flobufen metabolite and dapoxetine. In the former case, the homoallylic alcohol moiety (99 % ee) was converted into a five-membered lactone ring with good preservation of the optical purity, and the target compound, a flobufen metabolite, was obtained in 95 % ee. In the latter case, the homoallylic alcohol moiety (97 % ee) was transformed over several steps into a 3-aminopropanol moiety. During the course of the synthesis, the gradual loss of optical purity was observed, and the target compound, dapoxetine, was obtained in 85 % ee. The enantioselective allylation of an aromatic aldehyde to give the corresponding homoallylic alcohol was the key step in the syntheses of a flobufen metabolite and dapoxetine. In the first case, the homoallylic moiety was converted into a chiral five-membered lactone ring. In the second case, it was transformed into a chiral 1,3-amino alcohol moiety. Copyright
- Hessler, Filip,Korotvicka, Ales,Necas, David,Valterova, Irena,Kotora, Martin
-
supporting information
p. 2543 - 2548
(2014/05/06)
-
- Carica papaya lipase catalysed resolution of β-amino esters for the highly enantioselective synthesis of (S)-dapoxetine
-
An efficient synthesis of the (S)-3-amino-3-phenylpropanoic acid enantiomer has been achieved by Carica papaya lipase (CPL) catalysed enantioselective alcoholysis of the corresponding racemic N-protected 2,2,2-trifluoroethyl esters in an organic solvent. A high enantioselectivity (E > 200) was achieved by two strategies that involved engineering of the substrates and optimization of the reaction conditions. Based on the resolution of a series of amino acids, it was found that the structure of the substrate has a profound effect on the CPL-catalysed resolution. The enantioselectivity and reaction rate were significantly enhanced by switching the conventional methyl ester to an activated trifluoroethyl ester. When considering steric effects, the substituted phenyl and amino groups should not both be large for the CPL-catalysed resolution. The mechanism of the CPL-catalysed enantioselective alcoholoysis of the amino acids is discussed to delineate the substrate requirements for CPL-catalysed resolution. Finally, the reaction was scaled up, and the products were separated and obtained in good yields (≥ 80 %). The (S)-3-amino-3- phenylpropanoic acid obtained was used as a key chiral intermediate in the synthesis of (S)-dapoxetine with very high enantiomeric excess (> 99 %). A carica papaya lipase catalysed resolution of N-protected β-phenylalanine esters has been developed. High enantioselectivity was achieved by two strategies that involved engineering of the substrates and optimization of the reaction conditions. After 50 % conversion, the products were separated and used as key chiral intermediates for the synthesis of (S)-dapoxetine with > 99 % ee. Copyright
- You, Pengyong,Qiu, Jian,Su, Erzheng,Wei, Dongzhi
-
p. 557 - 565
(2013/03/13)
-
- Stereoselective synthesis of (S)-dapoxetine: A chiral auxiliary mediated approach
-
An imidazolidin-2-one chiral auxiliary mediated acetate aldol reaction was explored in the enantioselective synthesis of (S)-dapoxetine (SSRI). The diastereoselective aldol adduct was transformed to highly enantiopure (S)-dapoxetine with overall good yield.
- Khatik, Gopal L.,Sharma, Ratnesh,Kumar, Varun,Chouhan, Mangilal,Nair, Vipin A.
-
p. 5991 - 5993
(2013/10/22)
-
- Asymmetric total synthesis of (S)-dapoxetine
-
A concise asymmetric total synthesis of (S)-dapoxetine from commercially available 3-chloropropiophenone is described. The key step includes a highly stereoselective amination of chiral benzylic ether, with the retention of stereochemistry, using chlorosu
- Kim, Sun Joo,Jeon, Tae Hong,Min, Im Sook,Kim, In Su,Jung, Young Hoon
-
supporting information; experimental part
p. 3680 - 3682
(2012/09/25)
-
- Simple and efficient synthesis of (S)-dapoxetine
-
A refinement in the synthetic strategy for (S)-dapoxetine 1 is described. The key features of synthetic strategy include (a) a Sharpless asymmetric epoxidation reaction and regioselective reductive ring opening of a 2,3-epoxy alcohol to elaborate the hydroxy-bearing stereogenic center at benzylic position; (b) regioselective functionalization of 1-naphthol and amine functionality through Mitsunobu procedures; and (c) Eschweiler-Clarke reductive methylation condition to access the target molecule.
- Sasikumar,Nikalje, Milind D.
-
experimental part
p. 3061 - 3067
(2012/08/27)
-
- SOLID DAPOXETINE
-
The present invention provides racemic dapoxetine solid, process for its preparation and pharmaceutical compositions comprising it. The present invention also provides S-enantiomer of dapoxetine solid, process for its preparation and pharmaceutical compositions comprising it.
- -
-
Page/Page column 4
(2011/06/16)
-
- PROCESSES FOR THE PREPARATION OF (+)-N,N-DIMETHYL-2-[1-(NAPHTHALENYLOXY) ETHYL] BENZENE METHANAMINE AND INTERMEDIATES THEREOF
-
The present invention relates to processes for the preparation of S(+)-N,N-dimethyl-2-[1-(naphthalenyloxy)ethyl]benzene methanamine and intermediates thereof. More particularly the present invention relates to preparation of the compound 3(S)-(+)-N,N-dimethylamino-3-phenyl propanol useful as intermediate in the synthesis of pharmaceutically active compounds.
- -
-
-
- Highly efficient, enantioselective syntheses of (S)-(+)- and (R)-(-)-dapoxetine starting with 3-phenyl-1-propanol
-
(Chemical Equation Presented) A highly efficient, enantioselective sequence has been developed for the synthesis of (S)- and (R)-dapoxetine. The pathways involve the intermediacy of the 6-membered-ring sulfamate esters 4, which were generated by Du Bois asymmetric C-Hamination reactions of the prochiral sulfamate 3, catalyzed by the chiral dirhodium(II) complexes. During the course of our research, the absolute configuration of the enantiomer of 4-pheny[1,2,3]oxathiazinane 2,2-dioxide (4r), prepared by the Du Bois asymmetric C-H amination reaction of 3 and the Rh2(S-nap)4 catalyst, is determined to be R and not S as was originally reported.
- Kang, Soyeong,Lee, Hyeon-Kyu
-
supporting information; experimental part
p. 237 - 240
(2010/04/06)
-
- Stereoselective chemoenzymatic preparation of β-amino esters: Molecular modelling considerations in lipase-mediated processes and application to the synthesis of (S)-dapoxetine
-
A wide range of optically active 3-amino-3-arylpropanoic acid derivatives have been prepared by means of a stereoselective chemoenzymatic route. The key step is the kinetic resolution of the corresponding β-amino esters. Although the enzymatic acylations of the amino group with ethyl methoxyacetate showed synthetically useful enantioselectivities, the hydrolyses of the ester group catalyzed by lipase from Pseudomonas cepacia have been identified as the optimal processes concerning both activity and enantioselectivity. The enantiopreference of this lipase in these reactions has been explained, at the molecular level, by using a fragment-based approach in which the most favoured binding site for a phenyl ring and the most stable conformation of the 3-aminopropanoate core nicely match the (S)-configuration of the major products. The conversion and enantioselectivity values of the enzymatic reactions have been compared in order to understand the influence of the different substitution patterns present in the phenyl ring. This chemoenzymatic route has been successfully applied to the preparation of a valuable intermediate in the synthesis of (S)-dapoxetine, which has been chemically synthesised in excellent optical purity.
- Rodriguez-Mata, Maria,Garcia-Urdiales, Eduardo,Gotor-Fernandez, Vicente,Gotor, Vicente
-
experimental part
p. 395 - 406
(2010/06/15)
-
- PROCESS FOR PREPARING DAPOXETINE
-
This invention relates to a new process for preparation of enantiomerically pure dapoxetine or an acid addition salt thereof i.e. S(+)-N,N-dimethyl-2-[2-(naphthalenyl oxy)ethyl]benzenemethanamine hydrochoride, a potent serotonin re-uptake inhibitor (SSRI), which comprises resolving racemic (±)-dapoxetine i.e. (±)- N,N-dimethyl-2-[2- (naphthalenyloxy)ethyl] benzene methanamine with a chiral acid so as to obtain salt of the chiral acid and (+)-dapoxetine, substantially free from (-)-dapoxetine.
- -
-
Page/Page column 8; 11
(2010/11/30)
-
- Enantioselective synthesis of (S)-dapoxetine
-
An efficient enantioselective synthesis leading directly to (+)-(S)-dapoxetine has been described for the first time using a Sharpless asymmetric dihydroxylation, Barton-McCombie deoxygention, and Mitsunobu reaction as the key steps.
- Siddiqui, Shafi A.,Srinivasan, Kumar V.
-
p. 2099 - 2103
(2008/02/11)
-
- Lipase-catalyzed resolution of chiral 1,3-amino alcohols: application in the asymmetric synthesis of (S)-dapoxetine
-
The enzymatic resolution of 3-amino-3-phenylpropan-1-ol derivatives has been studied through acylation processes. Candida antarctica lipase A (CAL-A) has been identified as the best biocatalyst for the transesterification reaction of 3-amino-3-phenyl-1-tert-butyldimethylsilyloxy-propan-1-ol using ethyl methoxyacetate as acylating agent and tert-butyl methyl ether as solvent. This enzymatic study has allowed us to obtain a valuable intermediate for the production of (S)-dapoxetine, which has been synthesized in good overall yield and high enantiomeric excess.
- Torre, Oliver,Gotor-Fernandez, Vicente,Gotor, Vicente
-
p. 860 - 866
(2007/10/03)
-
