- Preparation method of flupiperidinol
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The invention belongs to the technical field of medicine preparation, and particularly relates to a preparation method of flupiperidinol. The preparation method of the fluoropiperidinol, provided by the invention, comprises the following steps of providing 4-(4-chlorphenyl)-4-piperidinol of which the purity is 99% or above, providing 4-chloro-1-(4-fluorophenyl)butan-1-one of which the purity is more than 99%, mixing the 4-(4-chlorphenyl)-4-piperidinol, 4-chloro-1-(4-fluorophenyl)butan-1-one, an alkaline substance and a catalyst, and carrying out a first substitution reaction to obtain a crudeproduct, and mixing the crude product with an organic solvent, and sequentially carrying out reflux and crystallization to obtain the flupiperidinol. The flupiperidinol prepared according to the preparation method provided by the invention has relatively high yield and purity.
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Paragraph 0089; 0095; 0098; 0104
(2021/03/24)
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- Direct C-H Arylation of Aldehydes by Merging Photocatalyzed Hydrogen Atom Transfer with Palladium Catalysis
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Herein, we report that merging palladium catalysis with hydrogen atom transfer (HAT) photocatalysis enabled direct arylations and alkenylations of aldehyde C-H bonds, facilitating visible light-catalyzed construction of a variety of ketones. Tetrabutylammonium decatungstate and anthraquinone were found to act as synergistic HAT photocatalysts. Density functional theory calculations suggested a Pd0-PdII-PdIII-PdI-Pd0 pathway and revealed that regeneration of the Pd0 catalyst and the photocatalyst occurs simultaneously in the presence of KHCO3. This regeneration features a low energy barrier, promoting efficient coupling of the palladium catalytic cycle with the photocatalytic cycle. The work reported herein suggests great promise for further applications of HAT photocatalysis in palladium-catalyzed cross-coupling and C-H functionalization reactions to be successful.
- Chen, Guangying,Cheng, Gui-Juan,Guo, Bin,Li, Xiaobao,Ran, Chongzhao,Wang, Lu,Wang, Ting,Wei, Jun-Jie,Zheng, Caijuan,Zheng, Chao
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p. 7543 - 7551
(2020/08/21)
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- Mn-Enabled Radical-Based Alkyl-Alkyl Cross-Coupling Reaction from 4-Alkyl-1,4-dihydropyridines
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Highly efficient alkylation of β-chloro ketones and their derivatives was achieved by means of domino dehydrochlorination/Mn-enabled radical-based alkyl-alkyl cross-coupling reaction. In situ-generated α,β-unsaturated ketones and their analogues were identified as the reaction intermediates. Known bioactive compounds, such as melperone and azaperone, could be easily prepared from β-chloropropiophenone in two steps.
- Wang, Jie,Pang, Yu-Bo,Tao, Na,Zeng, Run-Sheng,Zhao, Yingsheng
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p. 15315 - 15322
(2019/11/19)
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- Manganese-Catalyzed Electrochemical Deconstructive Chlorination of Cycloalkanols via Alkoxy Radicals
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A manganese-catalyzed electrochemical deconstructive chlorination of cycloalkanols has been developed. This electrochemical method provides access to alkoxy radicals from alcohols and exhibits a broad substrate scope, with various cyclopropanols and cyclobutanols converted into synthetically useful β- and γ-chlorinated ketones (40 examples). Furthermore, the combination of recirculating flow electrochemistry and continuous inline purification was employed to access products on a gram scale.
- Allen, Benjamin D. W.,Hareram, Mishra Deepak,Seastram, Alex C.,McBride, Tom,Wirth, Thomas,Browne, Duncan L.,Morrill, Louis C.
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supporting information
p. 9241 - 9246
(2019/11/19)
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- Palladium and visible-light mediated carbonylative Suzuki-Miyaura coupling of unactivated alkyl halides and aryl boronic acids
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Herein, a simple and efficient method for the palladium-catalyzed carbonylation of aryl boronic acids with unactivated alkyl iodides and bromides under visible-light irradiation, ambient temperature and low CO-pressure is presented. Notably, the procedure uses readily available equipment and an inexpensive palladium catalyst to generate the key alkyl radical intermediate. These mild conditions enabled the synthesis of a range of functionalized aryl alkyl ketones including the antipsychotic drug, melperone.
- Roslin, Sara,Odell, Luke R.
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supporting information
p. 6895 - 6898
(2017/07/10)
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- Direct Aldehyde C-H Arylation and Alkylation via the Combination of Nickel, Hydrogen Atom Transfer, and Photoredox Catalysis
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A mechanism that enables direct aldehyde C-H functionalization has been achieved via the synergistic merger of photoredox, nickel, and hydrogen atom transfer catalysis. This mild, operationally simple protocol transforms a wide variety of commercially available aldehydes, along with aryl or alkyl bromides, into the corresponding ketones in excellent yield. This C-H abstraction coupling technology has been successfully applied to the expedient synthesis of the medicinal agent haloperidol.
- Zhang, Xiaheng,MacMillan, David W. C.
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supporting information
p. 11353 - 11356
(2017/08/30)
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- Iron-Catalyzed Radical Decarboxylative Oxyalkylation of Terminal Alkynes with Alkyl Peroxides
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An iron-catalyzed oxyalkylation of alkynes with alkyl peroxides as the alkylating reagents has been investigated. Alkyl peroxides are readily available from aliphatic acids and serve simultaneously as the alkylating reagents and internal oxidants. Primary, secondary, and tertiary alkyl groups of aliphatic acids were readily incorporated into C?C triple bonds and diverse α-alkylated ketones were synthesized. Mechanism studies revealed that this reaction involves highly reactive alkyl free radicals. A unique equilibrium between lauric acid and water catalyzed by the iron(III) catalyst was observed.
- Zhu, Xiaotao,Ye, Changqing,Li, Yajun,Bao, Hongli
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supporting information
p. 10254 - 10258
(2017/08/07)
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- Regioselective Synthesis of Carbonyl-Containing Alkyl Chlorides via Silver-Catalyzed Ring-Opening Chlorination of Cycloalkanols
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A novel and regioselective approach to carbonyl-containing alkyl chlorides via silver-catalyzed ring-opening chlorination of cycloalkanols is reported. Concurrent C(sp3)-C(sp3) bond cleavage and C(sp3)-Cl bond formation efficiently occur with good yields under mild conditions, and the chlorinated products are readily transformed into other useful synthetic intermediates and drugs. The reaction features complete regioselectivity, high efficiency, and excellent practicality. (Chemical Equation Presented).
- Huang, Feng-Qing,Xie, Jian,Sun, Jian-Guo,Wang, Yue-Wei,Dong, Xin,Qi, Lian-Wen,Zhang, Bo
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supporting information
p. 684 - 687
(2016/03/01)
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- Bimetallic nanosized solids with acid and redox properties for catalytic activation of C-C and C-H bonds
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A new approach is presented to form self-supported bimetallic nanosized solids with acid and redox catalytic properties. They are water-, air- and H2-stable, and are able to activate demanding C-C and C-H reactions. A detailed mechanistic study on the formation of the Ag-Fe bimetallic system shows that a rapid redox-coupled sequence between Ag+, O2 (air) and Fe2+ occurs, giving monodisperse Ag nanoparticles supported by O-bridged diatomic Fe3+ triflimides. The system can be expanded to Ag nanoparticles embedded within a matrix of Cu2+, Bi3+ and Yb3+ triflimide.
- Cabrero-Antonino, Jose R.,Tejeda-Serrano, María,Quesada, Manuel,Vidal-Moya, Jose A.,Leyva-Pérez, Antonio,Corma, Avelino
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p. 689 - 696
(2016/12/28)
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- A combined computational and experimental investigation of the oxidative ring-opening of cyclic ethers by oxoammonium cations
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The propensity of oxoammonium cations to facilitate the oxidative ring-opening of cyclic ethers to their corresponding distal hydroxy ketones is investigated. The reaction has been evaluated using experimental and computational methods to gain deeper insight into trends in reactivity.
- Loman, Jacob. J.,Carnaghan, Emma R.,Hamlin, Trevor A.,Ovian, John M.,Kelly, Christopher B.,Mercadante, Michael A.,Leadbeater, Nicholas E.
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p. 3883 - 3888
(2016/05/24)
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- The synthesis of ω-(2-aryl-1,3-dioxolan-2-yl)alkyl purine derivatives and their activity towards HIV reverse transcriptase
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Novel derivatives of 6-substituted purines were synthesized by alkylation of 6-substituted purines with various 2-(chloroalkyl)-2-aryl-1,3-dioxolanes and related compounds. Their inhibitory properties toward HIV reverse transcriptase were studied. The structure-activity relationship within the synthesized compounds was found.
- Komissarov,Valuev-Elliston,Ivanova,Kochetkov,Kritzyn
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- Synthesis of the ortho / meta / para isomers of relevant pharmaceutical compounds by coupling a Sonogashira reaction with a regioselective hydration
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Aryl ketones substituted in ortho, meta, and para position are prepared by a palladium-catalyzed Sonogashira reaction followed by a regioselective hydration of the so-formed alkyne with triflimidic acid or a gold catalyst, under catalytic conditions. This methodology opens a way to obtain substituted aryl alkyl ketones from readily available starting materials, haloarenes, and terminal alkynes. The syntheses of the different regioisomers of haloperidol, melperone, pipamperone, and ibuprofen are presented. Structure-activity relationships for these compounds are studied with dopaminergic and cyclooxigenase binding assays.
- Leyva-Perez, Antonio,Cabrero-Antonino, Jose R.,Rubio-Marques, Paula,Al-Resayes, Saud I.,Corma, Avelino
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p. 722 - 731
(2014/04/03)
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- Regioselective hydration of alkynes by iron(III) Lewis/Bronsted catalysis
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The triflimide iron(III) salt [Fe(NTf2)3] promotes the direct hydration of terminal and internal alkynes with very good Markovnikov regioselectivities and high yields. The enhanced carbophilic Lewis acidity of the FeIII cation mediated by the weakly-coordinating triflimide anion is crucial for the catalytic activity. The iron(III) metal salt can be recycled in the form of the OPPh3/[Fe(NTf2)3] system with similar activity and selectivity. However, spectroscopic and kinetic studies show that [Fe(NTf2)3] hydrolyzes under the reaction conditions and that catalytically less active BrAonsted species are formed, which points to a Lewis/Bronsted co-catalysis. This triflimide-based catalytic system is regioselective for the hydration of internal aryl-alkynes and opens the door to a new synthetic route to alkyl ketophenones. As a proof of concept, the synthesis of two antipsychotics Haloperidol and Melperone, with general butyrophenone-like structure, is shown. Just add water! The triflimide iron(III) salt [Fe(NTf2)3] promotes the direct hydration of terminal and internal alkynes with very good Markovnikov regioselectivities and high yields (see scheme). Copyright
- Cabrero-Antonino, Jose R.,Leyva-Perez, Antonio,Corma, Avelino
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supporting information; experimental part
p. 11107 - 11114
(2012/09/22)
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- Acylation of Grignard reagents mediated by N-methylpyrrolidone: A remarkable selectivity for the synthesis of ketones
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An efficient user-friendly method of acylation of Grignard reagents to selectively synthesize ketones is presented, which is assisted by simple amides such as NMP, or DMF. The present chemoselective method tolerates a variety of functional groups such as ketone, ester, nitrile and other functional groups.
- Gowda, Maravanhalli Sidde,Pande, Sushanth Sudhir,Ramakrishna, Ramesha Andagar,Prabhu, Kandikere Ramaiah
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supporting information; experimental part
p. 5365 - 5368
(2011/09/13)
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- Indium(III) trifluoromethanesulfonate as an efficient catalyst for the deprotection of acetals and ketals
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(Chemical Equation Presented) Acetals and ketals are readily deprotected under neutral conditions in the presence of acetone and catalytic amounts of indium(III) trifluoromethanesulfonate (0.8 mol %) at room temperature or mild microwave heating conditions to give the corresponding aldehydes and ketones in good to excellent yields.
- Gregg, Brian T.,Golden, Kathryn C.,Quinn, John F.
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p. 5890 - 5893
(2008/02/09)
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- 4-Arylcyclohexylamines
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The invention relates to novel 4-hydroxymethyl(acyloxymethyl and methyl)-4-arylcyclohexylamines embraced by the formula SPC1 Wherein Ar is an aromatic ring selected from the group consisting of phenyl and naphthyl, each of which has from zero through three substituents independently selected from the group consisting of fluorine, chlorine, bromine, lower alkyl of one through three carbon atoms, lower alkoxy of one through three carbon atoms, and lower alkylthio of one through three carbon atoms; Z is selected from the group consisting of hydrogen, hydroxy and lower acyloxy of one through four carbon atoms; ? is a generic expression denoting cis and trans stereoconfiguration and mixtures thereof, with the proviso that when the stereoconfiguration of the linkage connecting the cyclohexane ring and CH2 Z is cis to the amino group, the linkage connecting the cyclohexane and Ar rings is trans, and vice versa; R1 is selected from the group consisting of hydrogen and lower alkyl of one through three carbon atoms; R2 is selected from the group consisting of hydrogen, lower alkyl of one through three carbon atoms, EQU1 WHEREIN N IS 2 THROUGH 5 AND Ar has the same meaning as above; R1 and R2 taken together with --N is a saturated heterocyclic amino radical selected from the group consisting of unsubstituted and substituted pyrrolidino, piperidino, hexamethylenimino, morpholino and piperazino; and pharmacologically acceptable acid addition salts thereof. It also relates to intermediates and processes for the preparation of the aforesaid novel compounds (I) and novel derivatives thereof. The administration to humans and animals of the novel compounds (I) depresses their central nervous systems and lowers their blood pressures.
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- Piperazino-anilido compounds
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Novel 1,4-disubstituted piperazine compounds and pharmaceutical compositions incorporating such compounds in conjunction with orally, parenterally or rectally administrable pharmaceutically acceptable carriers are disclosed. These compounds have coronary vasodilating properties. Also disclosed are processes for preparing these compounds, and novel intermediate compounds used in such processes.
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