cas 623-73-4, Ethyl diazoacetate | Articles data

Articles about 623-73-4Total 62 be found

Article title
Article abstract
Author
Journal number and time
Download

-
-
La Forge et al.
p. 391
(1952)
Read Online

-
-
Scheiner
p. 4489
(1971)
Read Online

-
-
Clusius,Luehti
p. 445
(1957)
Read Online

Ethyl diazoacetate synthesis in flow
Ethyl diazoacetate is a versatile compound in organic chemistry and frequently used on lab scale. Its highly explosive nature, however, severely limits its use in industrial processes. The in-line coupling of microreactor synthesis and separation technology enables the synthesis of this compound in an inherently safe manner, thereby making it available on demand in sufficient quantities. Ethyl diazoacetate was prepared in a biphasic mixture comprising an aqueous solution of glycine ethyl ester, sodium nitrite and dichloromethane. Optimization of the reaction was focused on decreasing the residence time with the smallest amount of sodium nitrite possible. With these boundary conditions, a production yield of 20 g EDA day-1 was achieved using a microreactor with an internal volume of 100 μL. Straightforward scale-up or scale-out of microreactor technology renders this method viable for industrial application.
Delville, Marielle M.E.,Van Hest, Jan C. M.,Rutjes, Floris P.J.T.
p. 1813 - 1818
(2013)
Read Online

A pilot-scale synthesis of (1R)-trans-2-(2,3-dihydro-4-benzofuranyl) cyclopropanecarboxylic acid: A practical application of asymmetric cyclopropanation using a styrene as a limiting reagent
Asymmetric cyclopropanation of styrene 1 (as the limiting reagent) was demonstrated using excess ethyl diazoacetate and catalytic Ru(ip-Pybox). Selective hydrolysis of the resulting 90:10 trans:cis mixture of cyclopropane 4 generated cyclopropyl acid 2 as a 96:4 trans:cis mixture with 84% e.e. for the trans-cyclopropane. Further purification and enantiomeric enrichment was achieved by diastereoselective crystallization with (+)-dehydroabeitylamine to afford the (R,R)-isomer with ≥99.9% e.e in 60-65 M% yield starting from styrene 1.
Simpson, James H.,Godfrey, Jollie,Fox, Rita,Kotnis, Atul,Kacsur, David,Hamm, Jason,Totelben, Michael,Rosso, Victor,Mueller, Richard,Delaney, Edward,Deshpande, Rajendra P.
p. 3569 - 3574
(2003)
Read Online

CuSO4-catalyzed three-component reaction of α-diazo ester, water and isatin: An efficient approach to oxindole derivatives
A highly efficient three-component reaction of α-diazo ester, water and isatin was developed by using CuSO4 as the catalyst. In this reaction, water was used as both a reactant and the solvent. With this highly environmentally benign and economical protocol, a series of 3-hydroxyindolin-2- one derivatives were efficiently produced in good yields with moderate to high diastereoselectivities.
Jing, Changcheng,Shi, Taoda,Xing, Dong,Guo, Xin,Hu, Wen-Hao
p. 620 - 624
(2013)
Read Online

-
-
Womack,Nelson
p. 392
(1955)
Read Online

A Three-Component Reaction to Construct β-Aminonitroso-α-Diazocarbonyl Compounds under Metal-Free Conditions
A procedure for the transition-metal-free three-component reaction of 1,3,5-triazines, diazo compounds and tert-butyl nitrite has been described. This reaction goes through tandem nucleophilic attack to generate synthetically important β-aminonitroso-α-diazocarbonyl compounds in moderate to good yields. This protocol is distinguished by the use of readily available starting materials, wide substrate scope and operational simplicity. Notably, a N?N bond and a C?C bond were formed simultaneously. (Figure presented.).
Chen, Rongxiang,Lan, Jihong,Li, Feng,Liu, Lantao,Wang, Kai-Kai,Xu, Canran,Xue, Yinghui
supporting information

(2022/04/03)

B(C6F5)3-Catalyzed site-selective N1-alkylation of benzotriazoles with diazoalkanes
Alkylation of benzotriazoles is synthetically challenging, often leading to mixtures of N1 and N2 alkylation. Herein, metal-free catalytic site-selective N1-alkylation of benzotriazoles with diazoalkanes is described in the presence of 10 mol% of B(C6F5)3. These reactions provide N1-alkylated benzotriazoles in good to excellent yields and this protocol is successfully adapted to gram-scale syntheses as well as a derivative with antimicrobial activity.
Guo, Jing,Mandal, Dipendu,Stephan, Douglas W.,Wu, Yile,Zhao, Yunbo
supporting information
p. 7758 - 7761
(2021/08/13)

METHOD OF PRODUCING NITRO COMPOUND
PROBLEM TO BE SOLVED: To provide a production method which can efficiently provide a nitro compound in an industrial scale. SOLUTION: A method of producing a compound represented by formula (2) comprises using nitric acid to nitrate a compound represented by formula (1) in the presence of concentrated sulfuric acid that weighs 1.5-5.0 times more than the compound represented by formula (1). [In formulas (1) and (2), X1 and X2 are identical or different and represent halogen atoms, and R represents an optionally substituted 6-membered heterocyclic group.] SELECTED DRAWING: None COPYRIGHT: (C)2021,JPOandINPIT
-
Paragraph 0041

(2021/06/25)

PYRIMIDINE-BASED BICYCLES AS ANTIVIRAL AGENTS FOR THE TREATMENT AND PREVENTION OF HIV INFECTION
This invention relates to pyrimidine derivatives, having HIV replication inhibiting. The present invention provides new pyrimidine compounds, designed for the treatment and prevention of HIV-mediated diseases. The invention further relates to pharmaceutical compositions and drugs contained in them. The invention also relates to the use of abovementioned compounds for the treatment and/or prevention of HIV in subjects with HIV-infection (human immunodeficiency virus) or having risk of getting HIV-infection.
-
Page/Page column 72; 73; 78; 79; 81-83; 85-86; 88-89; 91-94; ...

(2021/08/27)

Catalytic Ring Expansion of Activated Heteroarenes Enabled by Regioselective Dearomatization
Catalytic ring expansion of activated heteroarenes through 1,4-dearomative addition of diazoacetates was established for the construction of various fused azepines by an elaborate control of the reaction kinetics at each step. The use of a silver catalyst was essential to drive the overall reaction for generating the desired seven-membered azepines. Because of the excellent substrate scope and selectivity, the developed methodology presents an innovative approach for the synthesis of multifused azepines, which are biologically relevant molecules.
Kim, Jiyoung,Yoo, Eun Jeong
supporting information
p. 4256 - 4260
(2021/06/28)

Catalytic C-C coupling of diazo compounds with arylboronic acids: Using surface modified sewage sludge as catalyst
A green, mild and efficient synthesis of diarylmethines using sewage sludge-derived carbonaceous materials (SW) by perchloric acid catalyzed coupling reactions between diazo compounds and arylboronic acids was developed. The reaction shows a high level of functional tolerance and a broad substrate scope. Furthermore, the highly selective 1,2-alkyl shift products were furnished through the sterically demanding R4, R5 migration of diazo compounds (3-diazochromanone). The structures of 1,2-shift products have been further confirmed by single-crystal X-ray analysis. Significantly, the synthesis of the core structures of darifenacin (a clinical drug for overactive bladder syndrome, OAB) and diclofensine (a stimulant drug showing antidepressant and monoamine reuptake inhibitor activity) further demonstrated the efficacy and synthetic potential of this method. This journal is
Huang, Fei,Huang, He,Hughes, Timothy,Xie, Yuxing,Xu, Jun,Yu, Yang,Zhang, Zhipeng
supporting information
p. 4165 - 4173
(2020/07/14)

Copper-catalyzed carbene insertion and ester migration for the synthesis of polysubstituted pyrroles
Copper-catalyzed carbene insertion/ester migration/cyclization of enaminones and α-diazo compounds occurred efficiently to afford 2-ester polysubstituted pyrroles under mild conditions in moderate-to-good yields. Substituent functionality was well tolerated and13C-labelled experiments demonstrated 1,2-ester migration during the reaction.
Li, Mingrui,Sun, Yiming,Xie, Yuxing,Yu, Yang,Huang, Fei,Huang, He
supporting information
p. 11050 - 11053
(2020/10/05)

Tridentate Nickel(II)-Catalyzed Chemodivergent C-H Functionalization and Cyclopropanation: Regioselective and Diastereoselective Access to Substituted Aromatic Heterocycles
A Schiff-base nickel(II)-phosphene-catalyzed chemodivergent C-H functionalization and cyclopropanation of aromatic heterocycles is reported in moderate to excellent yields and very good regioselectivity and diastereoselectivity. The weak, noncovalent interaction between the phosphene ligand and Ni center facilitates the ligand dissociation, generating the electronically and coordinatively unsaturated active catalyst. The proposed mechanisms for the reported reactions are in good accord with the experimental results and theoretical calculations, providing a suitable model of stereocontrol for the cyclopropanation reaction.
Nag, Ekta,Gorantla, Sai Manoj N. V. T.,Arumugam, Selvakumar,Kulkarni, Aditya,Mondal, Kartik Chandra,Roy, Sudipta
supporting information
p. 6313 - 6318
(2020/09/02)

Cross coupling of sulfonyl radicals with silver-based carbenes: A simple approach to β-carbonyl arylsulfones
A coupling reaction between sulfonyl radicals and silver-based carbenes has been well established. This simple radical-carbene coupling (RCC) process provided an efficient approach to a variety of β-carbonyl arylsulfones from sodium arylsulfinates and diazo compounds, and was characterized by wide substrate scope, easy scale-up, simple manipulation, accessible starting materials, and mild reaction conditions.
Li, Jingjing,Lian, Pengcheng,Wan, Xiaobing,Wang, Hanghang,Zheng, Yonggao
supporting information
p. 2163 - 2169
(2020/03/27)

A diazonium acetate continuous carbonylation method
The invention discloses a diazonium acetate continuous synthesis of method, the glycinate ester hydrochloride aqueous solution, sodium nitrite aqueous solution, organic solvent two-stage diazotisations synthesis reaction, the product through static layering, heavy oil gases low tank, water layer to extraction kettle; to increase the extraction in the extraction to continue after the layered, water layer to acidification [...], oil on the heavy gases low tank is combined to form the diazonium acetate solution. Acidification of the aqueous layer in the [...], acidified and reflux, cooling, resin adsorption, negative pressure jan zheng, dehydration and concentration, centrifugal obtained after sodium chloride wet-base and centrifugal mother liquor, centrifugal mother liquor returns to the acidification in the [...] mechanically, sodium chloride wet oestrogen drying to obtain the technical grade sodium chloride. The method of the invention so that the reaction is capable of adequately so as to obtain high yield, while at the same time reaction to produce the high salt-containing waste water by processing and then recovering the sodium chloride; and the experiment of the whole process continuous production. To realize the non-waste water, waste gas, slag discharge clean production.
-
Paragraph 0031-0032; 0034-0035; 0037-0038; 0040-0041

(2019/06/07)

Synthesis of spiro[2,3-dihydrofuran-3,3′-oxindole] derivatives: Via a multi-component cascade reaction of α-diazo esters, water, isatins and malononitrile/ethyl cyanoacetate
We report a green synthesis of spiro[2,3-dihydrofuran-3,3′-oxindole] derivatives which are of potential value in medicinal chemistry. We are able to access spiro[2,3-dihydrofuran-3,3′-oxindole] derivatives via a Cu(OTf)2-catalyzed or Cu(OTf)2/Rh2(OAc)4-cocatalyzed multi-component cascade reaction of α-diazo esters, water, isatins and malononitrile/ethyl cyanoacetate. The reaction can be accomplished in good to excellent yields (60-99%), and the structure of products 6a and 6k was supported by X-ray crystallography. The catalyst Cu(OTf)2 can be recycled 4 times without a sharp loss of the yield of 6a. 6q can be easily synthesized in gram scale. In brief, the reaction is characterized by step economy, a harmless solvent, and a recyclable catalyst.
Shi, Taoda,Teng, Shenghan,Wei, Yajie,Guo, Xin,Hu, Wenhao
supporting information
p. 4936 - 4940
(2019/09/30)

Interception of Secondary Amide Ylide with Sulfonamides: Catalyst-Controlled Synthesis of N-Sulfonylamidine Derivatives
A novel, secondary amide activation strategy has been developed through the in situ generation of ylides from amides and diazoacetates. Under the developed reaction conditions, Mn-catalyzed ylide formation and interception reaction by sulfonamide delivered a variety of N-sulfonylamidines. Notably, when highly active Zn(OTf)2 was used as the catalyst, further N-H insertion products were obtained. In contrast with traditional methods, our amide activation strategy is distinguished by accessible starting material, inexpensive catalyst, and broad substrate scope.
Chen, Jijun,Long, Wenhao,Yang, Yonggang,Wan, Xiaobing
supporting information
p. 2663 - 2666
(2018/05/22)

In situ generation of nitrile oxides from copper carbene and tert -butyl nitrite: Synthesis of fully substituted isoxazoles
Herein, we present a novel [3 + 2] cycloaddition reaction of β-keto esters with nitrile oxides, which were generated in situ from copper carbene and tert-butyl nitrite. This three-component reaction provides new methodology for the direct synthesis of fully substituted isoxazole derivatives, featuring mild reaction conditions, readily accessible starting materials and simple operation. The experimental studies and DFT calculations suggest that the reaction starts with the generation of the key intermediate nitrile oxides, followed by a [3 + 2] cycloaddition reaction of β-keto esters to give the final isoxazole products.
Chen, Rongxiang,Ogunlana, Abosede Adejoke,Fang, Shangwen,Long, Wenhao,Sun, Hongmei,Bao, Xiaoguang,Wan, Xiaobing
supporting information
p. 4683 - 4687
(2018/07/06)

In Situ Generation of Oxazole Ylide and Interception with Sulfonamide: Construction of Amidines Using Two Diazo Molecules
A novel generation of oxazole ylide and interception with sulfonamide have been well developed to construct fully substituted amidines. This copper-catalyzed four-component reaction incorporates two diazo molecules to target amidines and shows broad substrate scope, excellent functional groups tolerance and good to excellent yields.
Chen, Jijun,Long, Wenhao,Zhao, Yanwei,Li, Haiyan,Zheng, Yonggao,Lian, Pengcheng,Wan, Xiaobing
supporting information
p. 857 - 865
(2018/07/31)

Interception of Radicals by Molecular Oxygen and Diazo Compounds: Direct Synthesis of Oxalate Esters Using Visible-Light Catalysis
The synthesis of oxalate esters through a radical process, rather than the traditional ionic reaction, has been well developed in which the radicals induced by visible light are trapped by molecular oxygen and diazo compounds under room temperature. This reaction is operationally simple, mild, and shows broad substrate scopes in α-bromo ketones and diazo compounds.
Ma, Meihua,Hao, Weiwei,Ma, Liang,Zheng, Yonggao,Lian, Pengcheng,Wan, Xiaobing
supporting information
p. 5799 - 5802
(2018/09/12)

Au Nanoparticle-Catalyzed Insertion of Carbenes from α-Diazocarbonyl Compounds into Hydrosilanes
Supported Au nanoparticles on TiO2 catalyze the insertion of carbenes from α-diazocabonyl compounds into hydrosilanes. It is proposed that the transformation involves two modes of catalytic activation: formation of nucleophilic Au carbenes on the surface of nanoparticle via expulsion of N2 and activation of the Si-H bond of hydrosilane on Au nanoparticle, followed by coupling of the chemisorbed species. No external ligands or additives are required, while the process is purely heterogeneous, thus allowing the recycling and reuse of the catalyst.
Kidonakis, Marios,Stratakis, Manolis
supporting information
p. 4086 - 4089
(2018/07/15)

Rh(III)-Catalyzed Regio- and Chemoselective [4 + 1]-Annulation of Azoxy Compounds with Diazoesters for the Synthesis of 2H-Indazoles: Roles of the Azoxy Oxygen Atom
A Rh(III)-catalyzed tandem C-H alkylation/intramolecular decarboxylative cyclization of azoxy compounds with diazoesters for the synthesis of 3-acyl-2H-indazoles is disclosed. The azoxy instead of the azo group enables a distinct approach for cyclative capture, leading to a [4 + 1]-annulation rather than a classic [4 + 2] manner. The azoxy oxygen atom is traceless after annulation, and further removal from the product is not required. This reaction features a complete regioselectivity for unsymmetrical azoxybenzenes and a compatibility of monoaryldiazene oxides.
Long, Zhen,Wang, Zhigang,Zhou, Danni,Wan, Danyang,You, Jingsong
supporting information
p. 2777 - 2780
(2017/06/07)

Chemoenzymatic synthesis and antileukemic activity of novel C9- and C14-functionalized parthenolide analogs
Parthenolide is a naturally occurring terpene with promising anticancer properties, particularly in the context of acute myeloid leukemia (AML). Optimization of this natural product has been challenged by limited opportunities for the late-stage functionalization of this molecule without affecting the pharmacologically important α-methylene-γ-lactone moiety. Here, we report the further development and application of a chemoenzymatic strategy to afford a series of new analogs of parthenolide functionalized at the aliphatic positions C9 and C14. Several of these compounds were determined to be able to kill leukemia cells and patient-derived primary AML specimens with improved activity compared to parthenolide, exhibiting LC50values in the low micromolar range. These studies demonstrate that different O–H functionalization chemistries can be applied to elaborate the parthenolide scaffold and that modifications at the C9 or C14 position can effectively enhance the antileukemic properties of this natural product. The C9-functionalized analogs 22a and 25b were identified as the most interesting compounds in terms of antileukemic potency and selectivity toward AML versus healthy blood cells.
Tyagi, Vikas,Alwaseem, Hanan,O'Dwyer, Kristen M.,Ponder, Jessica,Li, Qi Ying,Jordan, Craig T.,Fasan, Rudi
p. 3876 - 3886
(2016/08/04)

Design, Synthesis, and Biological Evaluation of Pyrazole Derivatives
In this in vitro study, a series of novel pyrazole derivatives were designed, synthesized, and evaluated against five human cancer cell lines (PC3, A549, HL60, HCT116, and SW620) for their antiproliferative and p53-MDM2 binding inhibitory activities. Although biological evaluations showed that this series of compounds possessed weak p53-MDM2 inhibitory activities, most of them displayed moderate to potent antiproliferative activities against the tested cells lines. Compound 11c exhibited the best potency for MDM2 (FP-IC50 = 29.22 μm) and demonstrated antiproliferative activities in response to the five tested cell lines (IC50 = 4.09-16.82 μm). Compared with the positive control Nutlin-1, there was enhanced antiproliferative activity to p53-mutated or p53-deficient cell lines (SW620, HL60, and PC3).
Hu, Chunqi,Gao, Yali,Du, Wenting
p. 673 - 679
(2016/05/09)

Trifluoromethylthiolation and Trifluoromethylselenolation of α-Diazo Esters Catalyzed by Copper
α-Diazo esters are smoothly converted into the corresponding trifluoromethyl thio- or selenoethers by reaction with Me4NSCF3or Me4NSeCF3, respectively, in the presence of catalytic amounts of copper thiocyanate. This straightforward method gives high yields under neutral conditions at room temperature and is applicable to a wide range of functionalized molecules, including diverse α-amino acid derivatives. It is well-suited for the late-stage introduction of trifluoromethylthio or -seleno groups into drug-like molecules.
Matheis, Christian,Krause, Thilo,Bragoni, Valentina,Goossen, Lukas J.
supporting information
p. 12270 - 12273
(2016/08/24)

Copper-catalyzed oxygen atom transfer of N-oxides leading to a facile deoxygenation procedure applicable to both heterocyclic and amine N-oxides
Deoxygenation of various types of N-oxides including both heterocyclic and alkyl(aryl)amine derivatives has successfully been developed by the copper-catalyzed oxygen atom transfer using diazo compounds as the oxygen acceptor. The reaction proceeds smoothly over a broad range of substrates with excellent functional group tolerance under mild conditions. This journal is
Jeong, Jisu,Lee, Donggun,Chang, Sukbok
supporting information
p. 7035 - 7038
(2015/04/22)

Continuous flow synthesis of toxic ethyl diazoacetate for utilization in an integrated microfluidic system
An integrated microfluidic system for multiple reactions and separations of hazardous ethyl diazoacetate is presented. The integrated techniques include: a droplet technique for liquid-liquid and/or gas-liquid separation and in situ generation of the toxic reagent, a dual channel membrane technique based on a cheap polymeric microseparator for liquid-liquid separation, and a capillary microreactor for carrying out cascade reactions in a sequential and continuous manner.
Maurya, Ram Awatar,Min, Kyoung-Ik,Kim, Dong-Pyo
supporting information
p. 116 - 120
(2014/01/06)

Safe generation and direct use of diazoesters in flow chemistry
A safe and fast method for the production of β-hydroxy-α- diazoesters in continuous flow technology is described. The synthesis involves the formation of ethyl diazoacetate in situ and the addition to several aldehydes in a two-step continuous flow microreactor setup. Rhodium acetate catalyzes a subsequent 1,2-hydride shift to give access to β-keto esters in a three-step sequence. Georg Thieme Verlag Stuttgart · New York.
Müller, Simon T. R.,Smith, Daniel,Hellier, Paul,Wirth, Thomas
p. 871 - 875
(2014/04/03)

A simple criterion for gas chromatography/mass spectrometric analysis of thermally unstable compounds, and reassessment of the by-products of alkyl diazoacetate synthesis
Rationale: A principal limitation of gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS) is the thermal instability of analytes. We propose that the injector and column temperatures should not exceed the atmospheric pressure boiling point, without decomposition, of the highest homologue of the series being analyzed, instead of the time-consuming procedure of obtaining chromatograms using different temperatures. Methods: A series of thermally unstable diazocarbonyl compounds, alkyl diazoacetates (predicted limit of stability approx. 140 °C, the boiling point of ethyl diazoacetate), was selected for GC/MS analysis using standard equipment. Different GC separation conditions were selected so that the retention temperatures of target compounds were both below and above 140°C. Results: Analyzing alkyl diazoacetates within their thermal stability range permitted reanalysis of their typical synthesis by-products. No dialkyl fumarate or maleate impurities, principal decomposition products which have often been reported previously, were found. Instead, alkyl esters of glycolic acid nitrate, O2NOCH 2CO2R, and 'pseudo-dimeric' products, ROCO[C 2H3NO]CO2R, were discovered for the first time. Conclusions: Avoiding the decomposition of thermally unstable organic compounds during GC and/or GC/MS analysis requires estimating their degradation temperature limits. This limit can be estimated as being equal to the atmospheric pressure boiling point of the highest homologue in the homologous series under consideration that does not decompose on boiling. Copyright
Kornilova, Tatiana A.,Ukolov, Anton I.,Kostikov, Rafael R.,Zenkevich, Igor G.
p. 461 - 466
(2013/03/14)

NOVEL COMPOUNDS
This invention relates to compounds of formula I their use as positive allosteric modulators of mGlu5 receptor activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of neurological and psychiatric disorders associated with glutamate dysfunction such as schizophrenia or cognitive decline such as dementia or cognitive impairment. A, B, X, R1, R2, R3 have meanings given in the description.
-
Paragraph 0481; 0482; 0483

(2013/06/26)

NOVEL COMPOUNDS
This invention relates to compounds of formula I their use as positive allosteric modulators of mGlu5 receptor activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of neurological and psychiatric disorders associated with glutamate dysfunction such as schizophrenia or cognitive decline such as dementia or cognitive impairment. A, B, X, R1, R2, R3 have meanings given in the description.
-
Paragraph 0410; 0411; 0412

(2013/06/27)

1,2,4 -TRIAZOLES AS ALLOSTERIC MODULATORS OF MGLU5 RECEPTOR ACTIVITY FOR THE TREATMENT OF SCHIZOPHRENIA OF DEMENTIA
This invention relates to compounds of formula (I) their use as positive allosteric modulators of mGlu5 receptor activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of neurological and psychiatric disorders associated with glutamate dysfunction such as schizophrenia or cognitive decline such as dementia or cognitive impairment. A, B, X, R1, R2, R3 have meanings given in the description.
-
Page/Page column 97

(2013/06/27)

A macrolactonisation approach to the cembrane carbocycle of bielschowskysin
By judicious choice of a conformationally constraining unit to predispose cyclisation to a 15-membered ring, we present a straightforward strategy to a cembranolide precursor of bielschowskysin by the Sonogashira coupling of two readily prepared fragments (from d-glucose and l-malic acid) followed by a facile β-acylketene macrolactonisation reaction.
Yang, Eugene G.,Sekar, Karthik,Lear, Martin J.
supporting information
p. 4406 - 4408
(2013/07/26)

NOVEL PROCESSES FOR THE PREPARATION OF PHENYLCYCLOPROPYLAMINE DERIVATIVES AND USE THEREOF FOR PREPARING TICAGRELOR
Provided herein are novel processes for the preparation of phenylcyclopropylamine derivatives, which are useful intermediates in the preparation of triazolo[4,5-d]pyrimidine compounds. Provided particularly herein are novel, commercially viable and industrially advantageous processes for the preparation of a substantially pure ticagrelor intermediate, trans-(1R,2S)-2-(3,4-difluorophenyl)-cyclopropylamine. Provided further herein are novel acid addition salts of trans-(1R,2S)-2-(3,4-difluorophenyl)-cyclopropylamine, and process for their preparation. The intermediate and its acid addition salts are useful for preparing ticagrelor, or a pharmaceutically acceptable salt thereof, in high yield and purity.
-
Paragraph 0276; 0277

(2013/07/05)

NOVEL PROCESSES FOR THE PREPARATION OF PHENYLCYCLOPROPYLAMINE DERIVATIVES AND USE THEREOF FOR PREPARING TICAGRELOR
Provided herein are novel processes for the preparation of phenylcyclopropylamine derivatives, which are useful intermediates in the preparation of triazolo[4,5-d]pyrimidine compounds. Provided particularly herein are novel, commercially viable and industrially advantageous processes for the preparation of a substantially pure ticagrelor intermediate, trans-(1R,2S)-2-(3,4-difluorophenyl)-cyclopropylamine. Provided further herein are novel acid addition salts of trans-(1R,2S)-2-(3,4-difluorophenyl)-cyclopropylamine, and process for their preparation. The intermediate and its acid addition salts are useful for preparing ticagrelor, or a pharmaceutically acceptable salt thereof, in high yield and purity.
-
Page/Page column 45

(2012/01/14)

CONTINUOUS FLOW PROCESS FOR THE PRODUCTION OF DIAZO ESTERS
Processes for producing diazo ester derivatives in a single phase system in a continuous flow reactor.
-
Page/Page column 30-31

(2012/10/08)

Stability of diazocarbonyl compounds under the conditions of gas chromatography and chromatography-mass spectrometry analysis
The gas chromatographic analysis of alkyldiazoacetates N 2CHCO2R (R = CH3 - C4H9), α-aliphatic diazoketones RCOCHN2 (R = C3H 7, C5H11, and C9H19), and aryl-substituted diazoketones Ph (CH2)nCOCHN2 (n = 0-2) is shown to be possible when their retention temperatures are below the boiling points of compounds of this series at atmospheric pressure without decomposition (about 140°C). At higher temperatures occurs partial or complete decomposition of α-diazoketones in chromatographic columns to form ketenes. Among the impurities in the reaction mixtures at the diazotization of corresponding alkyl glycinates were identified for the first time the nitrate esters of glycolic acid O2NOCH2CO2R, as well as the dimeric products. All diazocarbonyl compounds and the impurities were characterized by mass spectra. For the first time their gas chromatographic retention indices were determined. Pleiades Publishing, Ltd., 2012.
Kornilova,Ukolov,Kostikov,Zenkevich
p. 1675 - 1685
(2013/02/23)

Synthesis of deuterium and C-13-labelled ethyl glycolate and their subsequent use in the synthesis of labelled analogues of the DNA adduct O 6-carboxymethyl-2′-deoxyguanosine
The adduct O6-carboxymethyl-2′-deoxyguanosine (O 6CMdG) is of importance as it has been previously linked to high red meat diet in humans, and as yet, a liquid chromatography-mass spectrometry (LC-MS) method has not been developed due to lack of appropriate standards. The synthesis of the deuterated and C-13 analogues required the use of [ 2H2]- and [13C2]ethyl glycolate to label the carboxymethyl moiety of O6CMdG. [2H 2]Ethyl glycolate was synthesised via acid hydrolysis of ethyl diazoacetate using deuterated solvents (59% yield), whilst [13C 2]ethyl glycolate was synthesised from [13C 2]glycine in a three-step procedure (35% yield). The labelled ethyl glycolates were then used to synthesise [2H2]- and [ 13C2]O6CMdG for future use as internal standards in the LC-MS analysis of biological samples.
Moore, Sharon A.,Shuker, David E. G.
experimental part
p. 855 - 858
(2012/03/26)

Synthesis of 3-alkoxy/aryloxy - Lactams using diazoacetate esters as ketene precursors under photoirradiation
3-Alkoxy/aryloxy - lactams are synthesized in satisfactory to good yields from the reaction of imines and alkyl/aryl di-azoacetates under photoirradiation conditions. Typically, trans - lactams are obtained as the major products from linear imines using the current method. By contrast, the corresponding thermal reaction of imines and alkoxy/aryloxyacetyl chlorides, or their equivalents, in the presence of triethylamine affords cis - lactams as the major or exclusive products. The formation of trans - lactams from linear imines is attributed to isomerization of the imines from their trans-isomers into syn-isomers under UV irradiation. The reported method represents a metal-free and neutral approach for the synthesis of 3-alkoxy/aryloxy - lactams. Georg Thieme Verlag Stuttgart New York.
Qi, Hengzhen,Yang, Zhanhui,Xu, Jiaxi
scheme or table
p. 723 - 730
(2011/04/24)

PROCESS FOR THE PRODUCTION OF CYCLOPROPANE DERIVATIVES
A process for the preparation of a cyclopropane derivative of Formula (I), by reacting an olefin of Formula (II), with a carbene of the formula :CR1 R2, in a reaction vessel, optionally in the presence of a solvent, wherein, R1 and R2 are each independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocyclyl, -C(O)R7 or -NR82; R3, R4, R5 and R6 are each independently hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, aryl, aryloxy, heteroaryl, heterocyclyl, carbocyclyl, heterocyclyl, -C(O)R9, -NR102, -SR11, -S(O)R11, or -SO2R11, or R3 and R6 are as defined above and R4 and R5 together form a ring, which ring is carbocyclyl, heterocyclyl, aromatic or heteroaromatic; R7 is hydrogen, hydroxy, C1-C6 alkyl, C1-C6 alkoxy, aryl, aryloxy, heteroaryl or -NR102; R8 is hydrogen, C1-C6 alkyl, C1 -C6 alkenyl, aryl, heteroaryl, carbocyclyl or heterocyclyl; R9 is hydrogen, hydroxy, C1-C6 alkyl, C1 -C6 alkoxy, aryl, aryloxy or heteroaryl; R10 is hydrogen, C1 -C6 alkyl, C2-C6 alkenyl, aryl, heteroaryl, carbocyclyl, heterocyclyl or C(O)R12; R11 is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, aryl, heteroaryl, carbocyclyl or heterocyclyl; and R12 is hydrogen, hydroxy, C1-C6 alkyl, C1-C6 alkoxy, aryl, or aryloxy, in the presence of copper metal or copper oxide, wherein the process is a continuous process.
-
Page/Page column 18

(2010/06/15)

A Phosphine-mediated conversion of azides into diazo compounds
-
Myers, Eddie L.,Raines, Ronald T.
body text
p. 2359 - 2363
(2009/09/24)

PROCESS FOR PRODUCTION OF TRANS-2,2-DIMETHYL- 3-FORMYLCYCLOPROPANE CARBOXYLIC ACID ESTER
A process for production of a trans-2,2-dimethyl-3-formylcyclopropanecarboxylic acid ester comprising: (A) a step of obtaining a mixture containing a trans-2,2-dimethyl-3-(hydroxymethyl)cyclopropanecarboxylic acid ester, (B) a step of conducting an oxidation treatment of the mixture obtained in the step (A) to obtain a mixture containing a crude trans-2,2-dimethyl-3-formylcyclopropanecarboxylic acid ester, (C) a step of contacting the mixture obtained in the step (B) with an aqueous alkali metal hydrogen sulfite solution to obtain an alkali metal salt of a trans-2,2-dimethyl-3-[(hydroxy)(sulfo)methyl]cyclopropanecarboxylic acid ester, and (D) a step of contacting the alkali metal salt obtained in the above-mentioned step (C) with a base or the like to obtain a trans-2,2-dimethyl-3-formylcyclopropanecarboxylic acid ester.
-
Page/Page column 9-10

(2009/06/27)

Kilogram synthesis of a selective serotonin reuptake inhibitor
Process development of a selective serotonin reuptake inhibitor (1) is described. The synthesis features Nishiyama catalystmediated asymmetric cyclopropanation of vinyl indole 2 with ethyldiazoacetate to install the trans-disubstituted cyclopropane. The active pharmaceutical ingredient (1) was prepared in 13 chemical steps with 9 isolations and proceeded in an overall yield of 34%. ? 2008 American Chemical Society.
Anthes, Robert,Bello, Osagie,Benoit, Serge,Chen, Chien-Kuang,Corbett, Elisabeth,Corbett, Richard M.,DelMonte, Albert J.,Gingras, Stephane,Livingston, Robert,Sausker, Justin,Soumeillant, Maxime
p. 168 - 177
(2013/01/03)

Facile and efficient way to synthesize the radical cyclization precursor methyl 3-(tert-butyl((E)-3-(2,2-diphenylcyclopropyl)-2-propenyl)amino)-3-oxo-2- (phenylseleno)propanoate for kinetic research
Methyl 3-(tert-butyl((E)-3-(2,2-diphenylcyclopropyl)-2-propenyl)amino)-3- oxo-2-(phenylseleno)propanoate was prepared in 10 steps in good to excellent yield using benzophenone and hydrazine hydrate as the starting materials. Copyright Taylor & Francis Group, LLC.
Yu, Jindi,Lian, Gaoyan,Zhang, Danwei
p. 37 - 46
(2007/10/03)

Highly chemo- and stereoselective intermolecular coupling of diazoacetates to give cis-olefins by using Grubbs second-generation catalyst
Highly stereoselective formation of cis-2-ene-1,4-diesters by homo- and heterocoupling of α-diazoacetates in the presence of Grubbs second-generation catalyst is demonstrated. The dual reactivity of the catalyst in alkene metathesis and diazocoupling has been exploited in the synthesis of 12-26-membered macrocyclic dienyl dilactones by one-pot carbene dimerisation/ring-closing metathesis.
Hodgson, David M.,Angrish, Deepshikha
p. 3470 - 3479
(2008/02/08)

Diastereoselective synthesis of methylenecyclopropanes from chiral cyclopropene derivatives
(Chemical Equation Presented) Directed delivery: Chiral methylenecyclopropanes were prepared from cyclopropene derivatives upon reaction with Grignard reagents. A higher-order dependence of the reaction on the concentration of the Grignard reagent was revealed, and based on this finding, it was possible to reverse the regioselectivity of the process (see scheme; MEM = methoxyethoxymethyl).
Yang, Zhe,Xie, Xiaocong,Fox, Joseph M.
p. 3960 - 3962
(2007/10/03)

Synthesis of α-diazo-β-hydroxyesters through a one-pot protocol by phase-transfer catalysis: Application to enantioselective aldol-type reaction and diastereoselective synthesis of α-amino-β-hydroxyester derivatives
The one-pot synthesis of α-diazo-β-hydroxyesters from sodium azide under phase-transfer-catalyzed conditions has been achieved. This protocol includes three different chemical transformations promoted by a single catalyst in each step to give products in good to excellent yields. The reaction was applied to a catalytic asymmetric aldol-type reaction using α-diazoesters with aldehydes in the presence of a chiral quaternary ammonium salt and gave products with up to 81% ee. The diastereoselective transformation of the products to chiral α-amino-β-hydroxyester derivatives is also described.
Hasegawa, Kazuya,Arai, Shigeru,Nishida, Atsushi
p. 1390 - 1401
(2007/10/03)

PROCESS FOR PRODUCING PYRIDINE COMPOUND
The present invention provides a process for producing the pyridine compound [d]: [wherein R3 and R4 are as defined below], which has an excellent herbicidal activity, by making a pyridine compound [a]: [wherein R1 represents a C1-C6 alkoxy group, R3 represents a halogen atom, cyano group or nitro group, and R4 represents a hydrogen atom or halogen atom] react with an α-diazoester compound [f]:N2CHCOR1 [wherein R1 is defined above] in the presence of an acid.
-
Page 22

(2008/06/13)

Avermectin derivatives
Provided is a compound represented by the general formula (I) or a salt thereof: wherein, —XY— represents —CH═CH— and the like, between R2 and the carbon atom at 5-position represents a single bond or a double bond, R1 represents a lower alkyl group, a formyl group, a carboxyl group, a lower alkoxycarbonyl group (wherein a lower alkyl moiety of said lower alkoxycarbonyl group may be substituted with a heterocyclic group) and the like, and R1a represents a hydrogen atom, provided when R1 represents a lower alkoxycarbonyl group and the like, R1a may further represents a lower alkoxycarbonyl group and the like, when between R2 and the carbon atom at 5-position is a single bond, R2 represents a hydroxyl group and the like, and when between R2 and the carbon atom at the 5-position is a double bound, R2 combines with the carbon atom at 5-position to form a hydroxime group (—C(═NOH)) and the like, and R3 represents a hydroxyl group or a tri(lower alkyl)silyloxy group.
-
Page 12

(2011/05/18)

Process research, development, and pilot-plant preparation of clofencet, a novel wheat hybridizing agent: Lewis acid-catalyzed reaction of ethyl diazoacetate with 4-chlorophenyl hydrazonoacetaldehyde
Described are studies directed toward the chemical research and development of an alternative synthesis to 9, the penultimate intermediate of clofencet (1), a novel wheat-hybridizing agent. Retrosynthetic analyses as well as the results obtained from feasibility studies are detailed, leading to the successful development of an alternative process. The key features of the novel route are a method for preparing on-scale ethyl diazoacetate (28) in a safe and effective manner, and the Lewis acid-catalyzed reaction of 28 with hydrazonoacetaldehyde 29, affording β-ketoester 30. The synthesis is completed via propionylation of 30, acid-catalyzed cyclization of 31 to pyridazinecarboxylic acid ester 32, followed by saponification and isolation of carboxylic acid 9. The results and challenges of eight pilot-plant runs are reported. The baseline process developed produced over 45 kg of 9 in 43-45% yield.
Clark, Jerry D.,Heise, Jerald D.,Shah, Ajit S.,Peterson, James C.,Chou, Shine K.,Levine, Jeffrey,Karakas, Achilles M.,Ma, Yinong,Ng, Kin-Yin,Patelis, Lefteris,Springer, John R.,Stano, Don R.,Wettach, Richard H.,Dutra, Gerard A.
p. 176 - 185
(2013/09/04)

A new method for the synthesis of N-protected β-amino-α-keto esters from fluoroalkanesulfonylazides and α-keto esters
In the presence of a secondary amine, treatment of α-keto esters with fluoroalkanesulfonyl azides at room temperature afforded N-sulfonyl protected β-amino-α-keto esters in good to excellent yields. This reaction provided a novel, direct and convenient access to N-sulfonyl protected β-amino-α-keto esters from α-keto esters and fluoroalkanesulfonyl azides under mild conditions. However, the reaction of fluoroalkanesulfonyl azides with β-ketoester enamines afforded two products: N-fluoroalkanesulfonyl amidines and diazoacetate. The reaction mechanism is discussed.
Zhu, Shizheng,Jin, Guifang,Xu, Yong
p. 4389 - 4394
(2007/10/03)

A simple synthesis of fluoroalkyl substituted dihydrofurans by rhodium(II)-catalyzed 1,3-dipolar reactions
The rhodium(II)-catalyzed reactions of ethyl 2-diazo-fluoroalkylacetoacetate 1 with vinyl ethers have been studied. The reactions of 1a-e with isobutyl vinyl ethers afforded dihydrofuroates 3a-e in good to excellent yields. Further transformation of the dihydrofuroates by acid-catalyzed alcohol elimination could give α-fluoroalkyl-β-furoates readily. Similarly, stable diazo compounds 1a and b reacted with cyclic vinyl ethers to give 1,3-dipolar cycloaddition products. Interestingly, only vinyl C-H insertion compound was obtained concerning the reaction of 1a with 2,5-dimethylfuran. The reaction mechanism was also discussed.
Wang, Yanli,Zhu, Shizheng
p. 3383 - 3387
(2007/10/03)