- Feeding Carbonylation with CO2via the Synergy of Single-Site/Nanocluster Catalysts in a Photosensitizing MOF
-
Solar-driven carbonylation with CO2 replacing toxic CO as a C1 source is of considerable interest; however it remains a great challenge due to the inert CO2 molecule. Herein, we integrate cobalt single-site and ultrafine CuPd nanocluster catalysts into a
- Fu, Shanshan,Guo, Guang-Chen,Guo, Song,Lu, Tong-Bu,Yao, Shuang,Yuan, Wenjuan,Zhang, Zhi-Ming
-
p. 20792 - 20801
(2021/12/14)
-
- Photo-induced oxidative cleavage of C-C double bonds of olefins in water
-
The carbonyl compounds, synthesized by the oxidative cleavage of their corresponding olefins, are of great significance in organic synthesis, especially aryl ketones. We have developed a gentle and effective protocol, using acid red 94 as the organic metal-free photocatalyst, O2 as the oxidant, and water as the solvent. Under visible light irradiation, aryl ketone derivatives were obtained in moderate to excellent yields, showing good economic and environmental advantages.
- Zhang, Yilan,Yue, Xiaoguang,Liang, Chenfeng,Zhao, Jianming,Yu, Wenbo,Zhang, Pengfei
-
supporting information
(2021/08/27)
-
- Selective oxidation of alkenes to carbonyls under mild conditions
-
Herein, a practical and sustainable method for the synthesis of aldehydes, ketones, and carboxylic acids from an inexpensive olefinic feedstock is described. This transformation features very sustainable and mild conditions and utilizes commercially available and inexpensive tetrahydrofuran as the additive, molecular oxygen as the sole oxidant and water as the solvent. A wide range of substituted alkenes were found to be compatible, providing the corresponding carbonyl compounds in moderate-to-good yields. The control experiments demonstrated that a radical mechanism is responsible for the oxidation reaction.
- Huo, Jie,Xiong, Daokai,Xu, Jun,Yue, Xiaoguang,Zhang, Pengfei,Zhang, Yilan
-
supporting information
p. 5549 - 5555
(2021/08/16)
-
- Aryl aldiketone and synthesis method thereof
-
The invention discloses an aryl aldehyde ketone and a synthesis method thereof, wherein an aryl aldehyde is synthesized from cheap olefin as a raw material. A commercially available inexpensive olefin is used as a raw material, ether is used as an additive, molecular oxygen serves as a sole oxidizing agent, water is used as a solvent, and the aldehyde and ketone are synthesized by column chromatography under a photocatalytic condition. The invention has the advantages of mild reaction conditions, green and environmental protection, simple experimental operation, good reaction selectivity, high product yield and the like.
- -
-
Paragraph 0034
(2021/09/26)
-
- Palladium-Catalyzed Amide N-C Hiyama Cross-Coupling: Synthesis of Ketones
-
N-Acylglutarimides and arylsiloxanes reacted in the presence of Pd(OAc)2/PCy3, Et3N·3HF, and LiOAc to provide the corresponding arylketones in good yields. Aryl-, vinyl-, and alkyl-substituted N-acylglutarimides showed good activity in the coupling reactions of arylsiloxanes. The reaction had a broad substrate scope and showed good functional group tolerance. N-Benzoylsuccinimide and N-protected N-phenylbenzamides showed good activities in coupling reactions with phenylsiloxane. The employment of CuF2 as an activor afforded the decarbonylative products at 160 °C.
- Idris, Muhammad Aliyu,Lee, Sunwoo
-
supporting information
p. 9190 - 9195
(2020/11/18)
-
- A sodium trifluoromethanesulfinate-mediated photocatalytic strategy for aerobic oxidation of alcohols
-
A sodium trifluoromethanesulfinate-mediated photocatalytic strategy for the aerobic oxidation of alcohols has been developed for the first time, and the photoredox aerobic oxidation of secondary and primary alcohols provided the corresponding ketones and carboxylic acids, respectively, in high to excellent yields.
- Zhu, Xianjin,Liu, Can,Liu, Yong,Yang, Haijun,Fu, Hua
-
supporting information
p. 12443 - 12446
(2020/10/30)
-
- Synthesis method of fenofibrate drug molecules
-
The invention discloses a synthesis method of fenofibrate drug molecules. In the method, (1-methylethanol) 2-methyl-2-(4-carboxylphenoxy)propionate and 1-bromo-4-chlorobenzene are adopted as substrates; [Ir(dF(CF3)ppy)2(dtbbpy)]PF6 is used as a photocatalyst; triphenylphosphine is used as a deoxidizing agent; a nickel bromide ethylene glycol dimethyl ether complex is adopted as a nickel catalyst,4,4'-di-tert-butyl-2,2'-dipyridyl is adopted as a ligand and potassium phosphate and cesium carbonate are adopted as alkalis, reaction is performed under irradiation of a blue light lamp in a mixed solvent of N,N-dimethylformamide and acetonitrile to obtain a fenofibrate drug molecule compound. The method has the advantages of few steps, easily available raw materials and mild reaction conditions.
- -
-
Paragraph 0017-0019
(2020/05/08)
-
- A metal-free heterogeneous photocatalyst for the selective oxidative cleavage of CC bonds in aryl olefins: via harvesting direct solar energy
-
Selective cleavage of CC bonds is highly important for the synthesis of carbonyl containing fine chemicals and pharmaceuticals. Novel methodologies such as ozonolysis reactions, Lemieux-Johnson oxidation reaction etc. already exist. Parallel to these, catalytic methods using homogeneous catalysts also have been discovered. Considering the various advantages of heterogeneous catalysts such as recyclability and stability, couple of transition metal-based heterogeneous catalysts have been applied for this reaction. However, the pharmaceutical industries prefer to use metal-free catalysts (especially transition metal-free) to avoid further leaching in the final products. This is for sure a big challenge to an organic chemist and to the pharmaceutical industries. To make this feasible, a mild and efficient protocol has been developed using polymeric carbon nitrides (PCN) as metal-free heterogeneous photocatalysts to convert various olefins into the corresponding carbonyls. Later, this catalyst has been applied in the gram scale synthesis of pharmaceutical drugs using direct solar energy. Detailed mechanistic studies revealed the actual role of oxygen, the catalyst, and the light source.
- Das, Shoubhik,Hatami, Nareh,Jooss, Christian,Lange, Niklas Simon,Ronge, Emanuel,Schilling, Waldemar,Zhang, Yu
-
supporting information
p. 4516 - 4522
(2020/08/10)
-
- Synthesis and evaluation of fenofibric acid ester derivatives: Studies of different formulation with their bioavailability and absorption conditions
-
A series of fenofibric acid ester pro-drugs (JF-1-7) were synthesized. The pharmacokinetic properties of these pro-drugs were examined after oral administration to rats at a dose of 20 mg kg-1 to evaluate the relative bioavailability in rats. The bioavailability of the ester compounds, JF-1, 2, 3, 4, 5, 6, and 7, was significantly higher than that of fenofibrate. In particular, JF-2 proved to be most promising. The oral administration (20 mg kg-1) of JF-2 showed a relative bioavailability of approximately 272.8percent compared to fenofibrate.
- Lv, Zhixiang,Wang, Zhou,Xiao, Fuyan,Jin, Guofan
-
p. 280 - 287
(2020/01/03)
-
- Metal-free C-C bond formation: Via coupling of nitrile aimines and boronic acids
-
The challenges of developing sustainable methods of carbon-carbon bond formation remains a topic of considerable importance in synthetic chemistry. Capitalizing on the highly reactive nature of the nitrile imine 1,3-dipole, we have developed a novel metal-free coupling of this species with aryl boronic acids. Photochemical generation of a nitrile imine intermediate and trapping with a palette of boronic acids enabled rapid and facile access to a broad library of more than 25 hydrazone derivatives in up to 92% yield, forming a carbon-carbon bond in a metal free fashion. This represents the first reported example of direct reaction between boronic acids and a 1,3-dipole.
- Livingstone, Keith,Bertrand, Sophie,Mowat, Jenna,Jamieson, Craig
-
p. 10412 - 10416
(2019/11/20)
-
- Cobalt-catalyzed acylation-reactions of (hetero)arylzinc pivalates with thiopyridyl ester derivatives
-
A cobalt-catalyzed acylation reaction of various primary, secondary and tertiary alkyl, benzyl and (hetero)aryl S-pyridyl thioesters with (hetero)arylzinc pivalates is reported. The thioesters were prepared directly from the corresponding carboxylic acids under mild conditions, thus tolerating sensitive functional groups. Acylations of α-chiral S-pyridyl esters proceeded with very high stereoretention leading to optically enriched α-chiral ketones.
- Lutter, Ferdinand H.,Grokenberger, Lucie,Hofmayer, Maximilian S.,Knochel, Paul
-
p. 8241 - 8245
(2019/09/19)
-
- Palladium-Catalyzed Direct Oxidative Coupling of Iodoarenes with Primary Alcohols Leading to Ketones: Application to the Synthesis of Benzofuranones and Indenones
-
In the present study, a palladium-catalyzed direct oxidative acylation through cross-dehydrogenative coupling has been investigated, utilizing readily available primary alcohols as acylating sources. Overall, this oxidative coupling proceeds via three distinct transformations such as oxidation, radical formation, and cross-coupling in one catalytic process. This protocol does not involve the assistance of a directing group or activation of the carbonyl group by any other means. Furthermore, this reaction made use of no toxic CO gas as carbonylating agent; instead, feedstock primary alcohols have been utilized as acylation source. Notably, the synthesis of benzofuranones and indenones is enabled. This strategy was also applied to the synthesis of n-butylphthalide, fenofibrate, pitofenone, and neo-lignan.
- Suchand, Basuli,Sreenivasulu, Chinnabattigalla,Satyanarayana, Gedu
-
p. 4832 - 4843
(2019/07/31)
-
- Transition-Metal-Free Carbonylative Suzuki-Miyaura Reactions of Aryl Iodides with Arylboronic Acids Using N-Formylsaccharin as CO Surrogate
-
Unprecedented, high yielding, transition-metal-free carbonylative Suzuki-Miyaura reactions of aryl iodides with arylboronic acids using N-formylsaccharin as CO surrogate have been developed. Notably, this general protocol was adapted to the synthesis of the triglyceride and cholesterol regulator drug, fenofibrate, and carbon-13 labeled biaryl ketone. (Figure presented.).
- Yu, Dezhong,Xu, Fangning,Li, Dan,Han, Wei
-
supporting information
p. 3102 - 3107
(2019/05/21)
-
- Ligand-free Palladium-Catalyzed Carbonylative Suzuki Coupling of Aryl Iodides in Aqueous CH3CN with Sub-stoichiometric Amount of Mo(CO)6 as CO Source
-
A new method for the synthesis of diaryl and heterodiaryl ketones has been established based on the palladium-catalyzed carbonylative Suzuki coupling approach with sub-stoichiometric Mo(CO)6 as CO source. Using 0.5 mol% of Pd(TFA)2 as catalyst, 0.5 equivalent of Mo(CO)6 as solid carbonyl reagent and 3 equivalent of K3PO4 as base, a wide range of functionalized (hetero)aryl iodides and (hetero)aryl boronic acids could smoothly proceed the carbonylative cross-coupling reaction in aqueous CH3CN at 50 °C, affording the corresponding ketones in good to excellent yields. The newly developed method was easy to operate under mild conditions with high efficiency. (Figure presented.).
- Sun, Nan,Sun, Qingxia,Zhao, Wei,Jin, Liqun,Hu, Baoxiang,Shen, Zhenlu,Hu, Xinquan
-
p. 2117 - 2123
(2019/03/28)
-
- COtab: Expedient and Safe Setup for Pd-Catalyzed Carbonylation Chemistry
-
Bench-stable tablets (COtabs) have been developed for the rapid and safe production of carbon monoxide. The tablets can be made in less than 5 min without the use of a glovebox and only require a stock solution of an amine base to liberate a specific quantity of CO in a two-chamber system. The COtabs were tested in five different carbonylation reactions and provided similar yields compared to literature procedures. Finally, a gram-scale reaction was conducted, as well as 13C-isotope labeling of the anticancer drug, olaparib.
- Collin, Hugo P.,Reis, Wallace J.,Nielsen, Dennis U.,Lindhardt, Anders T.,Valle, Marcelo S.,Freitas, Rossimiriam P.,Skrydstrup, Troels
-
supporting information
p. 5775 - 5778
(2019/08/26)
-
- 5-Bromo-norborn-2-en-7-one derivatives as a carbon monoxide source for palladium catalyzed carbonylation reactions
-
Norbornenone (5b), obtained from the reaction of 2,5-dimethyl-3,4-diphenylcyclopentadienone dimer (3) with bromomaleic anhydride (4b), provides an excellent base-triggered source of carbon monoxide for palladium-catalysed carbonylation reactions. Aminocarbonylation, ketoamide synthesis, and Suzuki-Miyaura reactions of aryl iodides carried out in a two-chamber reaction vessel gave good to excellent yields of carbonylated products.
- Payne, China M.,Cho, Kyulee,Larsen, David S.
-
p. 30736 - 30740
(2019/10/19)
-
- Fenofibrate preparation method
-
The invention belongs to the technical field of drug preparation, and specifically relates to a fenofibrate preparation method. The preparation method comprises following steps: adding fenofibric acidinto excess isopropanol; then adding a macroporous highly acidic cation exchange resin catalyst, and carrying out esterification reactions at a certain temperature until fenofibric acid is completelyconsumed to obtain fenofibrate; wherein isopropanol is used as a solvent and a reactant. Compared with the prior art, macroporous highly acidic cation exchange resin is taken as a catalyst, has the advantages of large specific surface, high surface activity, high selectivity, few side reactions, and no equipment corrosion, is insoluble to the reaction system, can be easily separated from the reaction system, and can be repeatedly used. The product purification and separation are simplified. The novel catalyst has a wide application prospect.
- -
-
Paragraph 0023; 0026-0028; 0031-0033; 0036-0037
(2019/05/15)
-
- A general approach to intermolecular carbonylation of arene C-H bonds to ketones through catalytic aroyl triflate formation
-
The development of metal-catalysed methods to functionalize inert C-H bonds has become a dominant research theme in the past decade as an approach to efficient synthesis. However, the incorporation of carbon monoxide into such reactions to form valuable ketones has to date proved a challenge, despite its potential as a straightforward and green alternative to Friedel-Crafts reactions. Here we describe a new approach to palladium-catalysed C-H bond functionalization in which carbon monoxide is used to drive the generation of high-energy electrophiles. This offers a method to couple the useful features of metal-catalysed C-H functionalization (stable and available reagents) and electrophilic acylations (broad scope and selectivity), and synthesize ketones simply from aryl iodides, CO and arenes. Notably, the reaction proceeds in an intermolecular fashion, without directing groups and at very low palladium-catalyst loadings. Mechanistic studies show that the reaction proceeds through the catalytic build-up of potent aroyl triflate electrophiles.
- Kinney, R. Garrison,Tjutrins, Jevgenijs,Torres, Gerardo M.,Liu, Nina Jiabao,Kulkarni, Omkar,Arndtsen, Bruce A.
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p. 193 - 199
(2018/02/06)
-
- Integrative Photoreduction of CO2 with Subsequent Carbonylation: Photocatalysis for Reductive Functionalization of CO2
-
Efficient conversion of CO2 into fuels and chemicals with solar energy would be promising, but also faces great challenge. In this context, we describe the photoreductive functionalization of CO2 to construct new C?C, C?N, and C?O bonds through the respective Pd-catalyzed Suzuki carbonylation, aminocarbonylation, and alkoxycarbonylation of aryl iodides with CO in situ generated through the photoreduction of CO2. This protocol opens up an alternative avenue for CO2 utilization by harnessing solar energy.
- He, Xing,Cao, Yu,Lang, Xian-Dong,Wang, Ning,He, Liang-Nian
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p. 3382 - 3387
(2018/09/14)
-
- Thiyl radical promoted chemo- and regioselective oxidation of CC bonds using molecular oxygen: Via iron catalysis
-
The first example of the thiyl radical promoted ligand-free iron-catalyzed oxidative cleavage of alkenes using molecular oxygen (1 atm) has been developed. The reaction proceeds under mild reaction conditions with high efficiency and high chemo- and regioselectivity. It features a broad substrate scope and excellent functional group compatibility, enabling facile access to valuable molecules for application in medicinal chemistry. Preliminary mechanistic studies reveal that a vital intermediate dioxetane might be involved in the reaction and a thiyl radical plays a synergistic role in facilitating the selective oxidation of the CC bond.
- Xiong, Baojian,Zeng, Xiaoqin,Geng, Shasha,Chen, Shuo,He, Yun,Feng, Zhang
-
supporting information
p. 4521 - 4527
(2018/10/17)
-
- Hydrogen bond directed aerobic oxidation of amines via photoredox catalysis
-
An application of H-bonding interactions for directing the α-C-H oxidation of amines to amides and amino-ketones catalyzed by an organic photocatalyst is reported. The high efficiency of this method is demonstrated by the aerobic oxidation of pyrrolidines, diarylamines and benzylamines bearing urea groups with high yields and a wide substrate scope.
- Wang, Hongyu,Man, Yunquan,Wang, Kaiye,Wan, Xiuyan,Tong, Lili,Li, Na,Tang, Bo
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p. 10989 - 10992
(2018/10/08)
-
- Copper-Catalyzed Oxidative Cleavage of Electron-Rich Olefins in Water at Room Temperature
-
A copper-catalyzed oxidative cleavage of electron-rich olefins into their corresponding carbonyl derivatives is described as an alternative to ozonolysis. The scope includes various precursors to aryl ketone derivatives, as well as oxidations of enol ethers bearing atypical alkyl and dialkyl substitution, the first of their kind among such metal catalyzed alkene cleavage reactions. The use of an inexpensive copper salt, room temperature conditions, an aerobic atmosphere, and water as the global reaction medium highlight the green features of this new method. Associated mechanistic investigations are also presented.
- Lippincott, Daniel J.,Trejo-Soto, Pedro J.,Gallou, Fabrice,Lipshutz, Bruce H.
-
supporting information
p. 5094 - 5097
(2018/09/13)
-
- Palladium-catalyzed synthesis of diaryl ketones from aldehydes and (hetero)aryl halides via C-H bond activation
-
We developed a palladium-catalyzed C-H transformation that enabled the synthesis of ketones from aldehydes and (hetero)aryl halides. The use of picolinamide ligands was key to achieving the transformation. Heteroaryl ketones, as well as diaryl ketones, were synthesized in good to excellent yields, even in gram-scale, using this reaction. Results of density functional theory (DFT) calculations support the C-H bond activation pathway.
- Wakaki, Takayuki,Togo, Takaya,Yoshidome, Daisuke,Kuninobu, Yoichiro,Kanai, Motomu
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p. 3123 - 3128
(2018/04/14)
-
- Efficient synthesis of esters through oxone-catalyzed dehydrogenation of carboxylic acids and alcohols
-
Since esters are important organic synthesis intermediates, an environmentally friendly oxone catalyzed-esterification of carboxylic acids with alcohols has been developed. A series of carboxylic acid esters are obtained in high yield. This strategy requires mild reaction conditions, providing an attractive alternative for the construction of valuable carbonyl esters. Electron-rich and electron-deficient groups are compatible with the standard conditions and a variety of substrates are demonstrated. Moreover, the reaction could easily be adapted to typical prodrugs, drugs and gram-scale synthesis.
- Hou, Fei,Wang, Xi-Cun,Quan, Zheng-Jun
-
supporting information
p. 9472 - 9476
(2019/01/03)
-
- Visible Light Copper Photoredox-Catalyzed Aerobic Oxidative Coupling of Phenols and Terminal Alkynes: Regioselective Synthesis of Functionalized Ketones via C C Triple Bond Cleavage
-
Direct oxidative coupling of phenols and terminal alkynes was achieved at room temperature by a visible-light-mediated copper-catalyzed photoredox process. This method allows regioselective synthesis of hydroxyl-functionalized aryl and alkyl ketones from simple phenols and phenylacetylene via C C triple bond cleavage. 47 examples were presented. From a synthetic perspective, this protocol offers an efficient synthetic route for the preparation of pharmaceutical drugs, such as pitofenone and fenofibrate.
- Sagadevan, Arunachalam,Charpe, Vaibhav Pramod,Ragupathi, Ayyakkannu,Hwang, Kuo Chu
-
p. 2896 - 2899
(2017/03/11)
-
- Synthesis of a polar phosphinoferrocene amidosulfonate ligand and its application in pd-catalyzed cross-coupling reactions of aromatic boronic acids and acyl chlorides in an aqueous medium
-
The reaction of [1′-(diphenylphosphino)ferrocenyl]methylamine (1), generated in situ from its hydrochloride and triethylamine, with 2-sulfobenzoic anhydride afforded an anionic phosphino-amide, which was isolated as a triethylammonium salt, Ph2PfcCH2NHCOC6H4SO3(HNEt3) (2; fc = ferrocene-1,1′-diyl). A similar reaction of 1 with phthalic anhydride only furnished the salt (Ph2PfcCH2NH3)[C6H4CO2H(CO2)]. When it was reacted with [PdCl2(MeCN)2] and [LNCPd(μ-Cl)]2 (LNC = 2-[(dimethylamino-κN)methyl]phenyl-κC1), compound 2 gave rise to the bis-phosphine complex [PdCl2(2-κP)2] and the bridge-cleavage product [LNCPdCl(2-κP)], respectively. An analogue of the latter complex containing 2′-amino-[1,1′-biphenyl]-2-yl-κ2N,C2 as the auxiliary chelating ligand, compound 8, was prepared in a similar manner from 2 and the respective Pd precursor. Finally, the reaction of 2 with [LNCPd(acac)] proceeded with the replacement of the acetylacetonate ligand (acac), affording a dipalladium complex featuring two phosphinosulfonate anions as the O,P-bridges, [LNCPd(μ(P,O)-Ph2PfcCH2NHCOC6H4SO3)]2, which was structurally characterized by single-crystal X-ray diffraction analysis. All of these Pd(II) complexes, especially compound 8, formed active catalysts for Pd-mediated cross-coupling of aromatic boronic acids with benzoyl chlorides to produce substituted benzophenones in toluene (benzene)-water biphasic mixtures. This particular coupling reaction was employed during the preparation of 4′-chloro-4-hydroxybenzophenone, which was in turn converted to fenofibrate, a generic drug widely used to reduce cholesterol levels in blood.
- ?koch, Karel,Císa?ová, Ivana,?těpni?ka, Petr
-
p. 3378 - 3387
(2016/10/21)
-
- Antilipemic method for the preparation of pharmaceutical fenofibrate
-
The invention relates to a preparation method of antilipemic fenofibrate. According to the method, an esterification reaction between fenofibrate acid and isopropanol is catalyzed by a dual-function catalyst magnetic nano-solid super acid integrating magnetic and catalytic performances; through a magnetic separation technology, the catalyst is separated and recovered from a reaction product, thus obtaining a target product at high yield. The method disclosed by the invention has the characteristics of being simple to operate, easy to separate the product and high in product yield, and the catalyst is non-corrosive, free from pollution, recoverable and recyclable, environmentally friendly, low in production cost, etc.; and the preparation method is of great significance in industrial production.
- -
-
Paragraph 0031; 0032
(2017/02/24)
-
- An intelligent temperature control, fenofibrate preparing method for remote monitoring
-
The invention discloses a method for preparing fenofibrate and specifically relates to a method for preparing fenofibrate by virtue of intelligent temperature control and remote monitoring. The method comprises the following steps: reacting by taking fenofibric acid and isopropanol as raw materials and concentrated sulfuric acid as a catalyst, and after the reaction of the raw materials in the presence of the catalyst is finished, performing water washing, neutralizing, water washing, distilling and purifying operations on the product to obtain the fenofibrate. Besides, toluene is taken as a water-carrying agent, the method has the advantages of mild reaction conditions, short reaction time, convenient after-treatment, low dosage of acid and alkali, few impurities, low environmental pollution, recycling of non-reacting fenofibric acid and the like; the product yield is above 85% and the production cost is low; as a result, the method for synthesizing the fenofibrate is efficient and environment-friendly, and is advantageous to large-scale industrial production.
- -
-
Paragraph 0018
(2017/03/14)
-
- Merging Photoredox and Nickel Catalysis: The Direct Synthesis of Ketones by the Decarboxylative Arylation of α-Oxo Acids
-
The direct decarboxylative arylation of α-oxo acids has been achieved by synergistic visible-light-mediated photoredox and nickel catalysis. This method offers rapid entry to aryl and alkyl ketone architectures from simple α-oxo acid precursors via an acyl radical intermediate. Significant substrate scope is observed with respect to both the oxo acid and arene coupling partners. This mild decarboxylative arylation can also be utilized to efficiently access medicinal agents, as demonstrated by the rapid synthesis of fenofibrate. The direct decarboxylative arylation of α-oxo acids has been achieved by synergistic visible-light-mediated photoredox and nickel catalysis. This method offers rapid entry to aryl and alkyl ketone architectures from simple α-oxo acid precursors via an acyl radical intermediate. Significant substrate scope is observed with respect to both the oxo acid and arene coupling partners.
- Chu, Lingling,Lipshultz, Jeffrey M.,Macmillan, David W. C.
-
p. 7929 - 7933
(2015/06/30)
-
- DECARBOXYLATIVE CROSS-COUPLING AND APPLICATIONS THEREOF
-
Methods described herein enable the production of numerous molecular species through decarboxylative cross-coupling via use of photoredox and transition metal catalysts. For example, methods described herein enable the production of numerous molecular species through decarboxylative cross-coupling via use of photoredox and transition metal catalysts. A method described herein, in some embodiments, comprises providing a reaction mixture including a photoredox catalyst, a transition metal catalyst, a coupling partner and a substrate having a carboxyl group. The reaction mixture is irradiated with a radiation source resulting in cross-coupling of the substrate and coupling partner via a mechanism including decarboxylation, wherein the coupling partner is selected from the group consisting of a substituted aromatic compound and a substituted aliphatic compound.
- -
-
Page/Page column 42
(2015/12/09)
-
- Transition-metal-free, ambient-pressure carbonylative cross-coupling reactions of aryl halides with potassium aryltrifluoroborates
-
We disclose an unprecedented transition-metal-free carbonylative cross coupling of aryl halides with potassium aryl trifluoroborates even at atmospheric pressure of carbon monoxide. This protocol is efficient, operationally simple, and shows wide scope with regard to both aryl halides and potassium aryl trifluoroborates containing a series of active functional groups.
- Jin, Fengli,Han, Wei
-
supporting information
p. 9133 - 9136
(2015/06/08)
-
- METHOD FOR PRODUCING PULVERIZED ORGANIC COMPOUND PARTICLE
-
Disclosed is a method for producing pulverized particles of a crystalline organic compound which is poorly water-soluble. Also disclosed is a pulverized organic compound particle produced by such a method. Specifically disclosed is a method for producing a poorly water-soluble organic compound particle for medical use, which is characterized in that a poorly water-soluble organic compound for medical use is mixed with a physiologically acceptable salt and a physiologically acceptable polyol, and subjected to wet milling. Also specifically disclosed is a poorly water-soluble organic compound particle for medical use, which is produced by such a production method.
- -
-
-
- Reversed-polarity synthesis of diaryl ketones through palladium-catalyzed direct arylation of 2-Aryl-1,3-dithianes
-
An umpolung approach to the synthesis of diaryl ketones has been developed based on in situ generation of acyl anion equivalents and their catalytic arylation. This method entails the base-promoted, palladium-catalyzed direct C-H arylation of 2- aryl-1,3-dithianes with aryl bromides. Use of ( SiMe3)2 (M=Li, Na) base results in reversible deprotonation of the weakly acidic dithiane. In the presence of a Pd(NiXantphos)-based catalyst and aryl bromide, cross-coupling of the metallated 2-aryl- 1,3-dithiane takes place under mild conditions (2 h at rt) with yields as high as 96%. The resulting 2,2- diaryl-1,3-dithianes were converted into diaryl ketones by either molecular iodine, N-bromo succinimide (NBS) or Selectfluor in the presence of water. The dithiane arylation/hydrolysis can be performed in a one-pot procedure to yield a variety of diaryl ketones in good to excellent yields. This method is suitable for rapid and large-scale synthesis of diaryl ketones. A one-pot preparation of anti-cholesterol drug fenofibrate (TriCor) has been achieved on 10.0 mmol scale in 86% yield.
- Yucel, Baris,Walsh, Patrick J.
-
p. 3659 - 3667
(2015/01/09)
-
- Reversed-polarity synthesis of Diaryl Ketones through palladium-catalyzed direct Arylation of 2-Aryl-1,3-dithianes
-
An umpolung approach to the synthesis of diaryl ketones has been developed based on in situ generation of acyl anion equivalents and their catalytic arylation. This method entails the base-promoted, palladium-catalyzed direct C-H arylation of 2- aryl-1,3-dithianes with aryl bromides. Use of MNACHTUNGTRENUNG( SiMe3)2 (M=Li, Na) base results in reversible deprotonation of the weakly acidic dithiane. In the presence of a Pd(NiXantphos)-based catalyst and aryl bromide, cross-coupling of the metallated 2-aryl- 1,3-dithiane takes place under mild conditions (2 h at rt) with yields as high as 96%. The resulting 2,2- diaryl-1,3-dithianes were converted into diaryl ketones by either molecular iodine, N-bromo succinimide (NBS) or Selectfluor in the presence of water. The dithiane arylation/hydrolysis can be performed in a one-pot procedure to yield a variety of diaryl ketones in good to excellent yields. This method is suitable for rapid and large-scale synthesis of diaryl ketones. A one-pot preparation of anti-cholesterol drug fenofibrate (TriCor) has been achieved on 10.0 mmol scale in 86% yield.
- Yucel, Baris,Walsh, Patrick J.
-
supporting information
p. 3659 - 3667
(2015/01/09)
-
- Carbonylative suzuki couplings of aryl bromides with boronic acid derivatives under base-free conditions
-
The carbonylative Suzuki-Miyaura reaction between aryl bromides and arylboronic acid equivalents is herein reported, using base-free conditions and a limited excess of carbon monoxide generated ex situ from stable CO-precursors. Under these conditions, unsymmetrical biaryl ketones were obtained in modest to excellent yields. This method was adapted to the synthesis of the triglyceride and cholesterol regulator drug, fenofibrate, and its 13C-labeled derivative in good yields from the appropriate CO-precursor.
- Bjerglund, Klaus M.,Skrydstrup, Troels,Molander, Gary A.
-
supporting information
p. 1888 - 1891
(2014/05/06)
-
- An air-tolerant approach to the carbonylative suzuki-miyaura coupling: Applications in isotope labeling
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Carbonylative Suzuki-Miyaura coupling conditions have been developed that proceed without the exclusion of oxygen and in the presence of nondegassed and nondried solvents. By adapting the method to a two-chamber setup, the direct handling of carbon monoxide, produced from stable CO precursors, is avoided. The protocol afforded the desired benzophenones with excellent functional group tolerance and in good yields. Substituting the CO precursor, in the CO-producing chamber, with its carbon-13 labeled version generated the corresponding carbon-13 labeled benzophenones. Finally, the developed system was applied in the synthesis and isotope labeling of two pharmaceuticals, nordazepam and Tricor.
- Ahlburg, Andreas,Lindhardt, Anders T.,Taaning, Rolf. H.,Modvig, Amalie E.,Skrydstrup, Troels
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p. 10310 - 10318
(2013/11/06)
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- Solid self-microemulsifying systems
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The present invention relates to a self-microemulsifying system, preferably comprising active pharmaceutical ingredient, and a medicine prepared therefrom. This invention also relates to a process for preparing a solid self-microemulsifying system. In addition, it relates to a use of the self-microemulsifying system and a use of microcrystalline cellulose in admixture with the self-microemulsifying system. Specifically it describes a process for preparing a self-microemulsifying system comprising dispersing microcrystalline cellulose in a solvent, wherein the solvent further contains a viscosity enhancer, mixing the solvent with a self-microemulsifying system and spray drying the obtained mixture. In addition It provides the process comprising mixing a solid support and self-microemulsifying system to form a primary mixture and further granulating said primary mixture with a solution or suspension of a granulation binder. Both processes remarkably enhance processability of the solid self-microemulsifying system. Product and medicine obtainable by said processes are also provided.
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- NOVEL METHOD OF SYNTHESIZING FENOFIBRATE
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A novel process for the synthesis of fenofibrate, includes reacting a metal salt of fenofibric acid with an isopropyl halide, in a solvent system composed of a mixture of dimethyl sulfoxide and a C2-C4 alkyl acetate. The process can be used on an industrial scale and makes it possible to obtain a fenofibrate of a quality in accordance with the Pharmacopoeia without the need for purification by recrystallization.
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Page/Page column 2-3
(2012/03/27)
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- PHARMACEUTICAL FORMULATION OF NANONISED FENOFIBRATE
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The invention relates to a pharmaceutical formulation of nanonised fenofibrate, to a method for preparing same, and to the uses thereof.
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- Method for Producing Fenofibrate
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Method for producing fenofibrate from fenofibric acid by in situ preparation of fenofibric acid chloride by means of the action of a chlorinating agent on the acid then by reaction with isopropanol without isolation of the acid chloride.
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Page/Page column 2
(2010/08/07)
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- COMPOSITIONS COMPRISING LIPOPHILIC ACTIVE COMPOUNDS AND METHOD FOR THEIR PREPARATION
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Compositions are provided comprising a lipophilic active compound, e.g., a human or veterinary drug or a nutraceutical, interwoven with a polymeric matrix formed by two or more polymers, wherein one of the polymers is an amphiphilic polymer and the other polymer is either an amphiphilic polymer with a different hydrophobic-hydrophilic balance or a hydrophilic polymer, and the active lipophilic compound has modified physicochemical properties. The composition forms colloidal nanodispersion upon contact with aqueous media.
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- Method for preparing pure fenofibrate
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A process for the preparation of fenofibrate is disclosed. The process, consisting in crystallisation in specific conditions from C1-C4 alcohols or ketones, allows to obtain fenofibrate having a polymeric impurity content lower than 0.5%.
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Page/Page column 4
(2008/06/13)
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- Treatment of skin conditions by use of PPAR alpha activators
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Disorders of the skin and mucous membrane that have a disrupted or dysfunctional epidermal barrier are treated or prevented by topical application of compounds that are either activators of the farnesoid X receptor, activators of the peroxisome proliferator-activated receptor alpha , and oxysterol activators of the LXR alpha receptor. The same compounds are also effective in treating disorders of epidermal differentiation and proliferation.
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- FXR, PPARA and LXRA activators to treat acne/acneiform conditions
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Acne vulgaris and acneiform skin conditions are treated by the application of compounds that is juvenile hormone III, 7-methyl-9-(3,3-dimethyloxiranyl)-3-methyl-2,6-nonadienoic acid methyl ester.
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- Process for the production of dry pharmaceutical forms and the thus obtained pharmaceutical compositions
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A process for the production of a solid dispersion of at least one therapeutic agent in a hydrophilic carrier having enhanced solubility in an aqueous media comprising dissolving at least one therapeutic agent in a volatile organic solvent containing a very hydrophilic polymer and evaporating the solvent to dryness; to form a co-precipitate of therapeutic agent and hydrophilic polymer. This invention relates to the resulting products and to their therapeutic method of use.
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- Process for the production of dry pharmaceutical forms and the thus obtained pharmaceutical compositions
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A process for the production of a solid dispersion of at least one therapeutic agent in a hydrophilic carrier having enhanced solubility in an aqueous media comprising dissolving at least one therapeutic agent in a volatile organic solvent containing a very hydrophilic polymer and evaporating the solvent to dryness to form a co-precipitate of therapeutic agent and hydrophilic polymer and the resulting products and their therapeutic method of use.
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- Method for the preparation of fibrates
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The present invention relates to a method for the preparation of fibrates of the formula I according to the mechanism: STR1 in which R1 represents especially a halogen atom (in particular F, Cl or Br, the preferred halogen atom being Cl) or an acetyl, (4-chlorophenyl)hydroxymethyl, 4-chlorobenzoyl or 2-(4-chlorobenzamido)ethyl group and R2 represents a C1 -C4 alkyl group in which the hydrocarbon chain is linear or branched, the reaction V+VI being carried out without a solvent.
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- Derivatives of phenoxyalkylcarboxylic acids
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The invention provides novel phenoxyalkylcarboxylic acids which are useful in therapy as metabolic regulators and in agriculture as selective herbicides.
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- Beclobrate and eniclobrate hydrochloride, new diphenylmethane derivatives as agents for lowering cholesterol and triglyceride levels. Part I: Synthesis and consideration of structure-activity relationships (author's transl)
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Within the course of a research project for finding new lipid-lowering substances with better therapeutic indices than the standard agent in use, various diphenylmethane derivatives were synthesized and tested with respect to their activity and toxicity. On the basis of these results Sgd 24774 (beclobrate) and Sgd 33374 (eniclobrate-hydrochloride) were selected for further investigation and clinical studies.
- Thiele,Ahmed,Jahn,Adrian
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p. 711 - 720
(2007/10/05)
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