- Green method for catalyzing deprotection of tetrahydropyrane ether into hydroxyl compound
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The invention provides a green method for catalyzing deprotection of tetrahydropyrane ether into hydroxyl compound, and belongs to the field of green organic chemistry. According to the method, under neutral, open and room-temperature conditions, acetonitrile is used as a reaction solvent, FeBr2 or FeBr3 is used as a catalyst, H2O2 is used as an oxidizing agent, and a tetrahydropyrane ether derivative is converted into a hydroxyl compound within a short time. According to the invention, the catalyst FeBr2 and FeBr3, the oxidizing agent H2O2 and the solvent acetonitrile used in the method are cheap and easy to obtain, the reaction time is short, the condition is mild, the method has wide functional group compatibility, post-treatment is simple, operation is easy, and the method is a current green, environment-friendly and safe method for deprotecting the tetrahydropyrane ether derivative into the hydroxyl compound and has wide application prospects.
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Paragraph 0026-0028
(2022/03/17)
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- Access to Trisubstituted Fluoroalkenes by Ruthenium-Catalyzed Cross-Metathesis
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Although the olefin metathesis reaction is a well-known and powerful strategy to get alkenes, this reaction remained highly challenging with fluororalkenes, especially the Cross-Metathesis (CM) process. Our thought was to find an easy accessible, convenient, reactive and post-functionalizable source of fluoroalkene, that we found as the methyl 2-fluoroacrylate. We reported herein the efficient ruthenium-catalyzed CM reaction of various terminal and internal alkenes with methyl 2-fluoroacrylate giving access, for the first time, to trisubstituted fluoroalkenes stereoselectively. Unprecedent TON for CM involving fluoroalkene, up to 175, have been obtained and the reaction proved to be tolerant and effective with a large range of olefin partners giving fair to high yields in metathesis products. (Figure presented.).
- Nouaille, Augustin,Pannecoucke, Xavier,Poisson, Thomas,Couve-Bonnaire, Samuel
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supporting information
p. 2140 - 2147
(2021/03/06)
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- Continuous-Flow Amide and Ester Reductions Using Neat Borane Dimethylsulfide Complex
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Reductions of amides and esters are of critical importance in synthetic chemistry, and there are numerous protocols for executing these transformations employing traditional batch conditions. Notably, strategies based on flow chemistry, especially for amide reductions, are much less explored. Herein, a simple process was developed in which neat borane dimethylsulfide complex (BH3?DMS) was used to reduce various esters and amides under continuous-flow conditions. Taking advantage of the solvent-free nature of the commercially available borane reagent, high substrate concentrations were realized, allowing outstanding productivity and a significant reduction in E-factors. In addition, with carefully optimized short residence times, the corresponding alcohols and amines were obtained in high selectivity and high yields. The synthetic utility of the inexpensive and easily implemented flow protocol was further corroborated by multigram-scale syntheses of pharmaceutically relevant products. Owing to its beneficial features, including low solvent and reducing agent consumption, high selectivity, simplicity, and inherent scalability, the present process demonstrates fewer environmental concerns than most typical batch reductions using metal hydrides as reducing agents.
- ?tv?s, Sándor B.,Kappe, C. Oliver
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p. 1800 - 1807
(2020/02/27)
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- Carbene-Catalyzed α-Carbon Amination of Chloroaldehydes for Enantioselective Access to Dihydroquinoxaline Derivatives
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An NHC-catalyzed α-carbon amination of chloroaldehydes was developed. Cyclohexadiene-1,2-diimines are used as amination reagents and four-atom synthons. Our reaction affords optically enriched dihydroquinoxalines that are core structures in natural products and synthetic bioactive molecules.
- Huang, Ruoyan,Chen, Xingkuan,Mou, Chengli,Luo, Guoyong,Li, Yongjia,Li, Xiangyang,Xue, Wei,Jin, Zhichao,Chi, Yonggui Robin
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supporting information
p. 4340 - 4344
(2019/06/14)
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- Chemical modification-mediated optimisation of bronchodilatory activity of mepenzolate, a muscarinic receptor antagonist with anti-inflammatory activity
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The treatment for patients with chronic obstructive pulmonary disease (COPD) usually involves a combination of anti-inflammatory and bronchodilatory drugs. We recently found that mepenzolate bromide (1) and its derivative, 3-(2-hydroxy-2, 2-diphenylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane bromide (5), have both anti-inflammatory and bronchodilatory activities. We chemically modified 5 with a view to obtain derivatives with both anti-inflammatory and longer-lasting bronchodilatory activities. Among the synthesized compounds, (R)-(–)-12 ((R)-3-(2-hydroxy-2,2-diphenylacetoxy)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octane bromide) showed the highest affinity in vitro for the human muscarinic M3 receptor (hM3R). Compared to 1 and 5, (R)-(–)-12 exhibited longer-lasting bronchodilatory activity and equivalent anti-inflammatory effect in mice. The long-term intratracheal administration of (R)-(–)-12 suppressed porcine pancreatic elastase-induced pulmonary emphysema in mice, whereas the same procedure with a long-acting muscarinic antagonist used clinically (tiotropium bromide) did not. These results suggest that (R)-(–)-12 might be therapeutically beneficial for use with COPD patients given the improved effects seen against both inflammatory pulmonary emphysema and airflow limitation in this animal model.
- Yamashita, Yasunobu,Tanaka, Ken-ichiro,Yamakawa,Asano,Kanda, Yuki,Takafuji,Kawahara, Masahiro,Takenaga, Mitsuko,Fukunishi, Yoshifumi,Mizushima
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supporting information
p. 3339 - 3346
(2019/06/18)
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- Synthesis of α-Substituted Primary Benzylamines through Copper-Catalyzed Cross-Dehydrogenative Coupling
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A copper-catalyzed route to α-substituted, primary benzylamines by C-H functionalization of alkylarenes is described. The method directly affords the amine hydrochloride salt. Catalyst loadings down to 0.1 mol % in combination with scalability, insensitivity to air and moisture, and no need for column chromatography makes the procedure highly practical. The facile synthesis of the racemate of a blockbuster drug highlights the relevance for the development of pharmaceuticals. Preliminary mechanistic data are also included.
- Kramer, S?ren
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- Between the synthesis of trifluoromethyl phenylpropanol (by machine translation)
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The present invention provides a hydrogenation reduction preparation trifluoromethyl phenylpropanol method. In the high pressure autoclave, incendiary as solvent, adding meta-trifluoromethyl cinnamyl alcohol, according to three fluorine methyl cinnamyl alcohol of the mass fraction of 5% - 30% proportion of hydrogenation catalyst KT - 02, to the high-pressure seal is nitrogen after the replacement, the hydrogen gas to the pressure 0.5 - 3.0 mpa and heating to 40 - 100 °C reaction 4 - 15 hours, can be trifluoromethyl cinnamic alcohol between fully converted to three fluorine methyl carbonate, and the product yield of the product can be up to 99% or more. The hydrogenation catalyst used in this invention KT - 02 and the price is low, stable, and safe operation, in order to its as a hydrogenation catalyst after the reaction is finished and convenient product separation. Synthesis method of the invention will be more suitable for industrialized production between trifluoromethyl phenylpropanol. (by machine translation)
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-
Paragraph 0008; 0009; 0010
(2017/11/16)
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- Preparation method of 3-(3'-trifluoromethyl phenyl)propanol
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The invention relates to a preparation method of 3-(3'-trifluoromethyl phenyl)propanol and solves the technical problems that preparation of 3-(3'-trifluoromethyl phenyl)propanol is complex to operate, a large number of reducing agents are consumed and the like in the prior art. The preparation method comprises the synthesis steps as follows: 3-(3-trifluoromethyl phenyl) propionic acid and organic amine react with halogenated formate in an organic solution to form mixed anhydride through activation, the mixed anhydride reacts with an alkali metal borohydride solution to produce the 3-(3'-trifluoromethyl phenyl)propanol. The invention aims to reduce 3-(3-trifluoromethylphenyl)propionic acid to 3-(3'-trifluoromethyl phenyl)propanol with a simple and efficient method.
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Paragraph 0044-0054
(2017/08/30)
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- A plug intermediate body west that card 3 - (3-trifluoromethyl phenyl) propanol method for the synthesis of (by machine translation)
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The invention discloses a plug intermediate body west that card 3 - (3-trifluoromethyl phenyl) propanol synthetic method, including: the trifluoromethyl benzaldehyde dissolved in a solvent, adding wittig agents and organic alkali, in 0-100 °C under a temperature condition after the reaction is complete, the post-processed to obtain 3 - (3-trifluoromethyl phenyl) 2-propen -1 alcohol; to 3 - (3-trifluoromethyl phenyl) 2-propen -1 catalyst Pd/C alcohol solution added in, and pressurized hydrogenation, in 0-60 °C under a temperature condition after the reaction is complete, the post-processed to obtain 3 - (3-trifluoromethyl phenyl) propanol. The preparation process of the present invention the easily obtained raw material used, the cost is low, and the reaction is controllable, the test operation is simplified, the operation is simple, is easy to deal with, high yield of the product, and can be operated continuously, is suitable for industrial production. (by machine translation)
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Paragraph 0017
(2016/11/17)
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- Metal-Free Enantioselective Oxidative Arylation of Alkenes: Hypervalent-Iodine-Promoted Oxidative C?C Bond Formation
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The enantioselective oxyarylation of (E)-6-aryl-1-silyloxylhex-3-ene was achieved using a lactate-based chiral hypervalent iodine(III) reagent in the presence of boron trifluoride diethyl etherate. The silyl ether promotes the oxidative cyclization, and enhances the enantioselectivity. In addition, the corresponding aminoarylation was achieved.
- Shimogaki, Mio,Fujita, Morifumi,Sugimura, Takashi
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p. 15797 - 15801
(2016/12/16)
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- Synthesis of amines from alcohols in a nonepimerizing one-pot sequence - Synthesis of bioactive compounds: Cinacalcet and dexoxadrol
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A general, mild, and chemoselective one-pot oxidation/imine-iminium formation/nucleophilic addition sequence allowing the N-alkylation of amines by alcohols is described. This metal-free, one-pot sequence produced a wide variety of amines in good yields and diastereoselectivities, without the epimerization of the enantioenriched amines or alcohols involved in the process. This method was applied to the syntheses of the biologically active compounds cinacalcet and dexoxadrol. Copyright
- Guerin, Claire,Bellosta, Veronique,Guillamot, Gerard,Cossy, Janine
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experimental part
p. 2990 - 3000
(2012/07/13)
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- A novel asymmetric synthesis of cinacalcet hydrochloride
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A novel route to asymmetric synthesis of cinacalcet hydrochloride by the application of (R)-tert-butanesulfinamide and regioselective N-alkylation of the naphthyl ethyl sulfinamide intermediate is described.
- Arava, Veera R.,Gorentla, Laxminarasimhulu,Dubey, Pramod K.
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p. 1366 - 1373
(2012/10/29)
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- PYRAZOLO-TETRAHYDROPYRIDINE DERIVATIVES AS OREXIN RECEPTOR ANTAGONISTS
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The invention relates to novel pyrazolo-tetrahydropyridines compounds and their use as orexin receptor antagonists.
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Page/Page column 23
(2011/02/18)
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- PROCESS FOR PREPARING CINACALCET AND PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
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The resent invention rovides a novel rocess for re arin cinacalcet of formula I and pharmaceutically acceptable salts thereof and process of purification. The present invention also provides novel nitrogen protected synthetic intermediates useful in the process of the present invention. Further, the present invention provides a novel substituted carbamate impurity and process of preparation thereof.
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Page/Page column 19
(2011/08/03)
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- A process for the preparation of cinacalcet and intermediates thereof
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The present invention relates to a process for the preparation of (R)-(1-Naphthalen-1-yl-ethyl)-[3-(3-trifluoromethyl-phenyl)-propyl]-amine or a salt thereof, in particular the hydrochloride, and intermediates useful in its synthesis.
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- PROCESS FOR THE PREPARATION OF CINACALCET AND INTERMEDIATES THEREOF
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The present invention relates to a process for the preparation of (R)-(1-Naphthalen-1-yl-ethyl)-[3-(3-trifluoromethyl-phenyl)-propyl]-amine or a salt thereof, in particular the hydrochloride, and intermediates useful in its synthesis.
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- METHOD FOR PRODUCING PHENYLALKANE-1-OLS
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The present invention relates to a process for preparing phenylalkan-1-ols in three stages, where an ester condensation in the presence of alkali metal or alkaline earth metal alcoholates is carried out in the first stage.
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Page/Page column 4
(2011/06/10)
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- 5,6,7,8-TETRAHYDRO-IMIDAZO[1,5-A]PYRAZINE COMPOUNDS
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The invention relates to 5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine derivatives of formula (I) wherein R1, R2, R3, and R4 are as described n the description, to salts, especially pharmaceutically acceptable salts thereof, and to the use of such compounds as medicaments; especially as orexin receptor antagonists.
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Page/Page column 20
(2011/05/08)
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- PROCESS FOR THE PREPARATION OF CINACALCET AND SALTS THEREOF, AND INTERMEDIATES FOR USE IN THE PROCESS
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There is provided a process for preparing a salt of the (R)- or (S)-isomer of 1- naphthylethylamine with mandelic acid or a derivative thereof, the process comprising reacting racemic 1-naphthylethylamine with mandelic acid or a derivative thereof to obtain the (R)- or (S)-isomer of 1-naphthylethylamine salt (III) with the acid. The salts also form an aspect of the present invention. There is also provided a salt of the (R)- or (S)-isomer of 1-naphthylethylamine with mandelic acid or a derivative thereof. There is also provided a process for preparing cinacalcet (I) or a salt thereof, the process comprising reacting an ester (II) with (R)-i-naphthylethylamine or a salt of (R)-i-naphthylethylamine and mandelic acid or a derivative thereof, to obtain cinacalcet, and optionally converting the cincalcet to a salt thereof.
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Page/Page column 19
(2010/09/18)
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- PROCESS FOR PREPARING CINACALCET AND PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
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The resent invention rovides a novel rocess for re arin cinacalcet of formula I and pharmaceutically acceptable salts thereof and process of purification. The present invention also provides novel nitrogen protected synthetic intermediates useful in the process of the present invention. Further, the present invention provides a novel substituted carbamate impurity and process of preparation thereof.
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Page/Page column 38
(2010/04/03)
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- AMINE COMPOUND AND PHARMACEUTICAL USE THEREOF
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Provided is a novel amine compound represented by the following formula (I) having a superior peripheral blood lymphocyte decreasing action and superior in the immunosuppressive action, rejection suppressive action and the like, which shows decreased side effects of, for example, bradycardia and the like, or a pharmaceutically acceptable acid addition salt thereof, or a hydrate thereof, or a solvate thereof. wherein each symbol is as defined in the specification.
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Page/Page column 49
(2010/04/25)
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- PROCESSES FOR PREPARING INTERMEDIATE COMPOUNDS USEFUL FOR THE PREPARATION OF CINACALCET
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The invention relates, in general, to an improved process for preparing compounds (e.g., 3-(3-trifluoromethylphenyl)propanal (Compound III, below)), which are key intermediates for the synthesis of cinacalcet, its salts and/or solvates thereof, as well as the use of such compounds prepared by such process for the preparation of cinacalcet and/or its salts or solvates.
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Page/Page column 4
(2010/11/03)
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- PYRAZOLO-TETRAHYDRO PYRIDINE DERIVATIVES AS OREXIN RECEPTOR ANTAGONISTS
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The invention relates to novel pyrazolo-tetrahydropyridines compounds and their use as orexin receptor antagonists.
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Page/Page column 11; 18
(2009/04/24)
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- 5,6,7,8-TETRAHYDRO-IMIDAZO[1,5-A]PYRAZINE COMPOUNDS
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The invention relates to 5,6,7,8-tetrahydro-imidazo[1,5- a]pyrazine derivatives of formula (I) wherein R1, R2, R3, and R4 are as described n the description, to salts, especially pharmaceutically acceptable salts thereof, and to the use of such compounds as medicaments; especially as orexin receptor antagonists.
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Page/Page column 43
(2010/01/30)
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- PROCESSES FOR THE PREPARATION OF CINACALCET
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There are described several processes for making a free base of cinacalcet. One of the described processes goes through an intermediate of the formula (II) where R1 and R2 are both hydrogen, or R1 and R2, together, form a double bond.
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Page/Page column 34-35
(2008/12/05)
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- PROCESS FOR PREPARING CINACALCET HYDROCHLORIDE
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Processes for preparing cinacalcet are provided.
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Page/Page column 27; 28
(2008/06/13)
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- Synthesis of Cinacalcet congeners
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Two related substances 1 and 2 of Cinacalet were prepared. Two racemic isomeric dihydronaphthalenes 1 and 2 were prepared from commercially available 5-hydroxytetralone in five linear steps. A key palladium-catalyzed double bond migration led to the synthesis of both isomers from the same starting material. Preparative chiral HPLC separation provided the enantiomerically pure materials. An asymmetric synthesis employing CBS reduction to furnish 1 was also developed.
- Wang, Xin,Chen, Ying,Crockett, Richard,Briones, Jorge,Yan, Tony,Orihuela, Carlos,Zhi, Benxin,Ng, John
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p. 8355 - 8358
(2007/10/03)
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- Asymmetric syntheses of (S)-Fenfluramine using Sharpless Epoxidation Methods
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We describe one synthesis of (S)-fenfluramine and several syntheses of its precursors (R)- and (S)-1-(meta-trifluoromethylphenyl)propan-2-ols.They were obtained from the asymmetric epoxidation of the primary allylic alcohol 5 and from the kinetic resolution with asymmetric epoxidation of teh secondary allylic alcohol 6.
- Goument, Bertrand,Duhamel, Lucette,Mauge, Robert
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p. 171 - 188
(2007/10/02)
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- Epoxides, amino alcohols, and aziridines as key intermediates in the asymmetric synthesis of (S)-fenfluramine
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The epoxides 3E, 3Z and 8 were obtained from the isomeric alkenes 2E, 2Z and 7.The epoxides were ring-opened by ethylamine in ethanol yielding mixtures of the amino alcohols 4E and 11E, 4T and 11T, and 9, respectively, which were transformed into the aziridines 5trans, 5cis and 12.The regiospecific Pd/C-catalyzed reduction of these aziridines gave fenfluramine 1.The three epoxides 3trans, 3cis and 8 were reduced regiospecifically into 1-propan-2-ol 6, a potent precursor to fenfluramine 1.The validity of our method for asymmettric synthesis has been demonstrated by a synthesis of (S)-fenfluramine 1 starting from the amino alcohol (S)-9.Keyword - fenfluramine / asymmetric synthesis / epoxide / amino alcohol / aziridine / regiospecific catalytic hydrogenation / 1-propan-2-ols
- Goument, B.,Duhamel, L.,Mauge, R.
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p. 459 - 466
(2007/10/02)
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