82769-75-3Relevant articles and documents
Amino alcohols using the optically active amino alcohol derivative bi- Nord complex boron - -
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Paragraph 0064; 0071-0076; 0274-0276; 0278-0280, (2021/04/16)
Disclosed are an amino alcohol-boron-binol complex as an intermediate, including Complex 3-1-1 shown below, and a method for preparing an optically active amino alcohol by using the same, wherein a racemic amino alcohol is resolved in an enationselective manner using a boron compound and a (R)- or (S)-binol, whereby an amino alcohol derivative with high optical purity can be prepared at high yield.
Synthetic method of dapoxetine and intermediate thereof
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Paragraph 0106-0109, (2020/03/09)
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.
5-hydroxytryptamine re-absorption inhibitor crystal form and preparation method thereof
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Paragraph 0045-0054, (2019/08/30)
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.
A method for preparing west reaches anchors the sandbank hydrochloride (by machine translation)
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Paragraph 0067; 0068; 0069, (2017/08/25)
The invention relates to the field of medicine, in particular to a method for preparing west reaches anchors the sandbank hydrochloride, specifically comprises the following steps: (1) in order to chiral L - phenylalanine ester hydrochloride as the starting material, the reduction to obtain intermediate II reduction system; (2) intermediate II poly formaldehyde or formaldehyde generating Eschweiler - Clark reaction, to obtain the intermediate III; (3) the intermediate III with 1 - fluorine naphthalene generating Williamson west reaches anchors the sandbankcheng Mi reaction to obtain the hydrochloride. The present invention relates to chiral L - phenylalanine ester hydrochloride as the raw material of the final product to avoid splitting, and the raw materials are easy to obtain, the price is relatively low, the conventional apparatus to meet the need of production, without the use of expensive, there is a toxic reagent, mild reaction conditions, pollution is small, easy to control, and is suitable for industrial production. (by machine translation)
Method for preparing dapoxetine hydrochloride
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Paragraph 0048-0049; 0095; 0097, (2017/07/22)
The invention discloses a method for preparing dapoxetine hydrochloride. The method comprises the following steps: subjecting (s)-3-amino-3-phenylpropionic acid or an ester thereof to a reduction reaction in a reduction system prepared from a hydroborate and a boron trifluoride complex, so as to obtain an intermediate 1, i.e. (s)-3-amino-3-phenylpropanol; subjecting the (s) intermediate 1 to an Eschweiler-Clark reaction with formic acid and formaldehyde, so as to obtain an intermediate 2; subjecting the intermediate 2 to a Williamson ether forming reaction with 1-fluoronaphthalene, so as to obtain a free alkali, i.e. (s)-N,N-dimethyl-3-(1-naphthyloxy)phenyl propyl amine; subjecting the free alkali to a salt forming reaction with alcohol-acyl chloride or a chloride thereof, a hydrochloric acid organic solution or hydrochloric acid gas, thereby obtaining dapoxetine hydrochloride. According to the method, the synthesis route is low in production cost, the reaction conditions are mild, all the materials are readily available, the raw materials are low in toxicity, the reaction is simple in operation and high in safety, and the product is high in purity and yield and is environmentally friendly, so that the method is applicable to industrial large-scale production.
Syntheses of a flobufen metabolite and dapoxetine based on enantioselective allylation of aromatic aldehydes
Hessler, Filip,Korotvicka, Ales,Necas, David,Valterova, Irena,Kotora, Martin
supporting information, p. 2543 - 2548 (2014/05/06)
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
Process for preparation of enantiomerically pure S-(+)-N, N-dimethyl-a-[2-(naphthalenyloxy)ethyl] benzenemethanamine
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Paragraph 0104; 0105, (2014/07/09)
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.
PROCESSES FOR THE PREPARATION OF (+)-N,N-DIMETHYL-2-[1-(NAPHTHALENYLOXY) ETHYL] BENZENE METHANAMINE AND INTERMEDIATES THEREOF
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, (2012/01/13)
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.
Stereoselective chemoenzymatic preparation of β-amino esters: Molecular modelling considerations in lipase-mediated processes and application to the synthesis of (S)-dapoxetine
Rodriguez-Mata, Maria,Garcia-Urdiales, Eduardo,Gotor-Fernandez, Vicente,Gotor, Vicente
experimental part, p. 395 - 406 (2010/06/15)
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.
An efficient formal synthesis of (S)-dapoxetine from enantiopure 3-hydroxy azetidin-2-one
Chincholkar, Pinak M.,Kale, Ajaykumar S.,Gumaste, Vikas K.,Deshmukh, Abdul Rakeeb A.S.
experimental part, p. 2605 - 2609 (2009/08/08)
An efficient formal synthesis of S-(+) dapoxetine starting from 3-hydroxy azetidin-2-one is described. The intermediate (S)-3-(dimethyl amino)-3-phenylpropan-1-ol was synthesized in enantiopure form starting with 3-hydroxy azetidin-2-one in seven steps.
