153294-00-9Relevant academic research and scientific papers
Mild Esterification of Carboxylic Acids via Continuous Flow Diazotization of Amines
Audubert, Clément,Lebel, Hélène
supporting information, p. 4407 - 4410 (2017/08/23)
A new continuous flow protocol for the diazotization of methylamine with 1,3-propanedinitrite in THF is reported. The synthesis of methyl esters was achieved in high yields from a variety of carboxylic acids in 20 min at 90 °C. Additionally, this protocol was extended to other aryl and alkyl amines, namely secondary amines, to produce various substituted esters in high yield using 2-MeTHF as a solvent. The reaction conditions were compatible with many functional groups, namely nitrogen-containing heterocycles, alkynes, alkenes, alcohols, and phenols. Mechanistic investigations reveal that the reaction appears to proceed through a transient diazonium species rather than a diazo intermediate.
Batch and Continuous-Flow One-Pot Processes using Amine Diazotization to Produce Silylated Diazo Reagents
Audubert, Clément,Gamboa Marin, Oscar Javier,Lebel, Hélène
supporting information, p. 6294 - 6297 (2017/05/19)
A novel synthesis of trimethylsilyldiazomethane (TMSCHN2) by diazotization of trimethylsilylmethylamine (TMSCH2NH2) is reported using batch and continuous flow synthesis. The latter affords a daily production of 275 g (2.4 mol) of TMSCHN2. Other silylated methylamines were also successfully reacted under the developed reaction conditions to furnish various silicon-bearing diazomethane reagents. The applicability of the process is highlighted by disclosure of batch and continuous flow one-pot esterification and 1,3-dipolar cycloaddition processes. Furthermore, the high-yielding esterification of carboxylic acids with silylated and substituted methylamines in continuous flow is disclosed. Finally, work-up and purification procedures are reported for the preparation of a 2-MeTHF solution of TMSCHN2, which can be used in rhodium-catalyzed methylenation and homologation reactions.
The Synthesis of Chiral α-Aryl α-Hydroxy Carboxylic Acids via RuPHOX-Ru Catalyzed Asymmetric Hydrogenation
Guo, Huan,Li, Jing,Liu, Delong,Zhang, Wanbin
, p. 3665 - 3673 (2017/09/11)
A ruthenocenyl phosphino-oxazoline-ruthenium complex (RuPHOX?Ru) catalyzed asymmetric hydrogenation of α-aryl keto acids has been successfully developed, affording the corresponding chiral α-aryl α-hydroxy carboxylic acids in high yields and with up to 97% ee. The reaction could be performed on a gram scale with a relatively low catalyst loading (up to 5000 S/C) and the resulting products can be transformed to several chiral building blocks, biologically active compounds and chiral drugs. (Figure presented.).
Kinetic resolution of mandelate esters via stereoselective acylation catalyzed by lipase PS-30
Chen, Peiran,Yang, Wenhong
, p. 2290 - 2294 (2014/04/17)
By using lipase PS-30 as catalyst, the kinetic resolution of a series of racemic mandelate esters has been achieved via stereoselective acylation. The value of kinetic enantiomeric ratio (E) reached up to 197.5. Substituent effect is briefly discussed.
HETEROCYCLIC COMPOUNDS AS MDM2 INHIBITORS FOR THE TREATMENT OF CANCER
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Page/Page column 129; 130, (2013/04/13)
The present invention provides MDM2 inhibitor compounds of Formula I or II, or the pharmaceutically acceptable salts thereof, wherein the variables are defined above, which compounds are useful as therapeutic agents, particularly for the treatment of cancers. The present invention also relates to pharmaceutical compositions that contain an MDM2 inhibitor.
Asymmetric synthesis and evaluation of a hydroxyphenylamide voltage-gated sodium channel blocker in human prostate cancer xenografts
Davis, Gary C.,Kong, Yali,Paige, Mikell,Li, Zhang,Merrick, Ellen C.,Hansen, Todd,Suy, Simeng,Wang, Kan,Dakshanamurthy, Sivanesan,Cordova, Antoinette,McManus, Owen B.,Williams, Brande S.,Chruszcz, Maksymilian,Minor, Wladek,Patel, Manoj K.,Brown, Milton L.
experimental part, p. 2180 - 2188 (2012/05/05)
Voltage-gated sodium channels are known to be expressed in neurons and other excitable cells. Recently, voltage-gated sodium channels have been found to be expressed in human prostate cancer cells. α-Hydroxy-α- phenylamides are a new class of small molecules that have demonstrated potent inhibition of voltage-gated sodium channels. The hydroxyamide motif, an isostere of a hydantoin ring, provides an active scaffold from which several potent racemic sodium channel blockers have been derived. With little known about chiral preferences, the development of chiral syntheses to obtain each pure enantiomer for evaluation as sodium channel blockers is important. Using Seebach and Frater's chiral template, cyclocondensation of (R)-3-chloromandelic acid with pivaldehyde furnished both the cis- and trans-2,5-disubsituted dioxolanones. Using this chiral template, we synthesized both enantiomers of 2-(3-chlorophenyl)-2-hydroxynonanamide, and evaluated their ability to functionally inhibit hNav isoforms, human prostate cancer cells and xenograft. Enantiomers of lead demonstrated significant ability to reduce prostate cancer in vivo.
Enantioselective iron-catalysed O-H bond insertions
Zhu, Shou-Fei,Cai, Yan,Mao, Hong-Xiang,Xie, Jian-Hua,Zhou, Qi-Lin
experimental part, p. 546 - 551 (2010/10/04)
The ready availability, low price and environmentally benign character of iron mean that it is an ideal alternative to precious metals in catalysis. Recent growth in the number of iron-catalysed reactions reported reflects an increasing demand for sustainable chemistry. Only a limited number of chiral iron catalysts have been reported and these have, in general, proven less enantioselective than other transition-metal catalysts, thus limiting their appeal. Here, we report that iron complexes of spiro-bisoxazoline ligands are highly efficient catalysts for asymmetric O-H bond insertion reactions. These complexes catalyse insertions into the O-H bond of a wide variety of alcohols and even water, with exceptional enantioselectivities under mild reaction conditions. The selectivities surpass those obtained with other transition-metal catalysts. This study should inspire and encourage the use of iron instead of traditional precious metals in the development of greener catalysts for catalytic asymmetric synthesis.
Catalytic asymmetric reaction with water: Enantioselective synthesis of α-hydroxyesters by a copper-carbenoid O-H insertion reaction
Zhu, Shou-Fei,Chen, Chao,Cai, Yan,Zhou, Qi-Lin
, p. 932 - 934 (2008/09/20)
(Chemical Equation Presented) Taking on water: A novel catalytic asymmetric metal-carbenoid insertion reaction with water has been developed with copper complexes of chiral spiro bisoxazoline ligands as catalysts. This reaction provides an efficient and practical procedure for preparing chiral α-hydroxyesters and acids starting from readily available materials in high yields and enantioselectivities. BArF- = [B{3,5-(CF3)2C6H3)} 4]-.
Enantioselective homoallyl-cyclopropanation of dibenzylideneacetone by modified allylindium halide reagents-rapid access to enantioenriched 1-styryl-norcarene
Lloyd-Jones, Guy C.,Wall, Philip D.,Slaughter, Jennifer L.,Parker, Alexandra J.,Laffan, David P.
, p. 11402 - 11412 (2007/10/03)
Dibenzylideneacetone (8) reacts with in situ-generated allylindium halide reagents to yield the product of a homoallyl-cyclopropanation reaction: 2-(3″-butenyl)-1,1-bis[(E)-2′-phenylethenyl]cyclopropane (9), which proceeds via step-wise cleavage of the C{double bond, long}O bond and delivery of two allyl fragments from the reagent. A range of enantiomerically enriched ligands have been tested as stoichiometric asymmetric modifiers for this process. Enantiopure compounds such as cinchona alkaloids, ephedra, aminoalcohols and tartaric acid derivatives, which have proven of utility as asymmetric modifiers for the indium-mediated allylation of aldehydes and ketones, were very inefficient in the process 8→9. However, mandelic acid derivatives, in particular mandelates, were found to be of significant potential. The absolute stereochemistry of the cyclopropane 9 has been determined by degradation to 1,1-dicarboxymethyl-2-butylcyclopropane, converging with an independent enantioselective synthesis starting from hexene. Under optimised conditions, viz. using allylindium iodide reagents and working-up with aqueous Na2SO3 to avoid iodine-mediated polymerisation, (S)-9 can be generated in 86% yield and with (S)-methyl mandelate as modifier useful enantiopurity (94/6 er) was observed. The cyclopropane product ((S)-9) undergoes RCM using standard conditions to afford a norcarene unit ((1S,6S)-1-(E)-2′-(phenylethenyl)-bicyclo[4.1.0]hept-2-ene) without loss of enantiopurity.
A METHOD FOR THE PRODUCTION OF CHIRAL SUBSTITUTED EPOXIDES
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Page/Page column 14, (2008/06/13)
A method for the production of chiral substituted epoxides of formula (I) wherein R represents a substituted C5-C20-aryl-, C5-C20-heterocycle or C1-C20-alkyl radical, R1 represents H or is
