116539-60-7Relevant articles and documents
Preparation method of duloxetine
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, (2021/09/26)
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.
Duloxetine hydrochloride salt of basic and duloxetine (by machine translation)
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, (2017/06/02)
[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)
Chemoenzymatic synthesis of (S)-duloxetine using carbonyl reductase from Rhodosporidium toruloides
Chen, Xiang,Liu, Zhi-Qiang,Lin, Chao-Ping,Zheng, Yu-Guo
, p. 82 - 89 (2016/02/23)
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.
Preparation method for chiral gamma-sec-amino-alcohol
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Paragraph 0286-0292, (2016/10/08)
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.
Method for the synthesis of duloxetine
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, (2016/10/07)
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.
A method for preparing duloxetine hydrochloride
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Paragraph 0030-0031, (2017/03/08)
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.
A method for preparing optically active 3-amino-1-propanol derivatives as an intermediate and a method for preparing (S)-duloxetine using the same
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, (2016/12/01)
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
Minimizing Aryloxy Elimination in RhI-Catalyzed Asymmetric Hydrogenation of β-Aryloxyacrylic Acids using a Mixed-Ligand Strategy
Li, Yang,Wang, Zheng,Ding, Kuiling
, p. 16387 - 16390 (2015/11/09)
The first example of efficient asymmetric hydrogenation of challenging β-aryloxyacrylic acids was realized using a RhI-complex based on the heterocombination of a readily available chiral monodentate secondary phosphine oxide (SPO) and an achiral monodentate phosphine ligand as the catalyst. Excellent enantioselectivities (92->99% ee) were achieved for a wide variety of chiral β-aryloxypropionic acids with minor aryloxy elimination in most cases. The resultant products were readily transformed into biologically active compounds through simple synthetic manipulations.
Total synthesis of fluoxetine and duloxetine through an in situ imine formation/borylation/transimination and reduction approach
Calow, Adam D. J.,Fernandez, Elena,Whiting, Andrew
, p. 6121 - 6127 (2014/08/05)
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.
