- Asymmetric Synthesis of Optically Active 3-Cyclohexene-1-carboxylic Acid Utilizing Lactic Ester as a Chiral Auxiliary in the Diastereoselective Diels–Alder Reaction
-
The optically active 3-cyclohexene-1-carboxylic acid was synthesized through a TiCl4-catalyzed diastereoselective Diels–Alder reaction utilizing lactic acid ester as a chiral auxiliary, which can be removed by washing with H2O. The (S)- and (R)-isomers were both derived from easily available ethyl l-lactate.
- Ochiai, Hidenori,Hayashi, Wakana,Nishiyama, Akira,Fujita, Ryunosuke,Kubota, Shunichi,Sasagawa, Miwa,Nishi, Tatsuya
-
supporting information
p. 1002 - 1009
(2022/02/09)
-
- Synthesis method of chiral fenoxanil
-
The invention relates to a synthesis method of chiral fenoxanil. The synthesis method of the chiral fenoxanil is characterized in that chiral ethyl lactate is subjected to sulfonylation reaction to obtain sulfonic acid ester; the sulfonic acid ester reacts with 2,4-dichlorophenol to generate 2-(2,4-dichlorophenoxy) ethyl propionate; the 2-(2,4-dichlorophenoxy) ethyl propionate and 2,-amino-2,3-dimethyl nitrile are subjected to ammonia ester exchange reaction to generate corresponding chiral fenoxanil, wherein the molar ratio of the 2-(2,4-dichlorophenoxy) ethyl propionate to the 2,-amino-2,3-dimethyl nitrile is 1:1 and the reaction temperature is 60 to 85 DEG C. The method is simple in synthesis route, hydrolysis and chlorination are not needed, little waste water and waste gas are generated, a high environmentally-friendly benefit is achieved, the production cost is greatly reduced, the condition is mild, the fenoxanil with optical chirality can be synthesized in an oriented mode by selecting different configuration of ethyl lactate, and important significance of further exploring the optical property of the fenoxanil is achieved.
- -
-
Paragraph 0028
(2017/02/28)
-
- PROCESS FOR PREPARING 2-FLUOROPROPIONALDEHYDE
-
A process comprising (i) providing a 2-fluoropropionic acid halide; (ii) hydrogenating the 2-fluoropropionic acid halide by contacting it with a heterogeneous hydrogenation catalyst in an atmosphere comprising hydrogen, obtaining a mixture comprising 2-fluoropropionic aldehyde.
- -
-
Page/Page column 29
(2016/03/12)
-
- Asymmetric synthesis and anti-protozoal activity of the 8,4′-oxyneolignans virolin, surinamensin and analogues
-
The asymmetric synthesis of 8,4′-oxyneolignans (-)-virolin, (-)-surinamensin and a number of analogues has been achieved. A divergent synthesis was used, with all compounds being elaborated from a single chiral aldehyde derived from ethyl lactate. In the
- Rye, Claire E.,Barker, David
-
p. 240 - 248
(2013/03/28)
-
- Synthesis of optically active α-(nonafluoro-tert-butoxy)carboxylic acids
-
Three novel α-(nonafluoro-tert-butoxy)carboxylic esters were synthesized by two methods: the Mitsunobu reaction of optically active (S)-α-hydroxycarboxylic esters and the Williamson synthesis starting from the corresponding O-mesyl derivatives. Both procedures from ethyl (S)-lactate resulted in the formation of a fluorous optically active (R)-lactic acid ester derivative, while the reactions from methyl (S)-mandelate took place with racemization. The proposed mechanism of this racemization is described. The conversion of methyl (S)-phenyllactate under Mitsunobu conditions was also stereospecific, but the reaction of its O-mesyl derivative yielded a mixture of substitution and elimination products. The optical purity of the α-(nonafluoro-tert-butoxy)carboxylic acids prepared by the hydrolysis of the above esters was determined by 1H NMR spectroscopy.
- Csóka, Tamás,Nemes, Anikó,Szabó, Dénes
-
p. 1730 - 1733
(2013/04/10)
-
- 2,4-DIAMINO-6,7-DIHYDRO-5H-PYRROLO[2,3]PYRIMIDINE DERIVATIVES AS FAK/Pyk2 INHIBITORS
-
The invention relates to a novel class of 2,4-diamino-6,7-dihydro-5H-pyrrolo[2,3]pyrimidine derivatives as a FAK and/or Pyk2 inhibitor, to a process for their preparation, and to a composition thereof, as well as to use of the compounds for the inhibiting FAK and/or Pyk2 and method for the treatment of a FAK and/ or Pyk2 mediated disorder or disease.
- -
-
Page/Page column 38
(2012/07/27)
-
- Iron(III)-catalyzed halogenations by substitution of sulfonate esters
-
A novel halogenation reaction from sulfonates catalyzed by iron(III) is described. The reaction can be performed as a stoichiometric or a catalytic version. This reaction provides a convenient strategy for the efficient access to structurally diverse secondary chlorides, bromides and iodides. The stereochemical course of the reaction is governed by the substrate and the experimental conditions. Secondary alcohols modified as quisylates or pysylates are substantially more reactive. Aliphatic quisylates proceed with overall inversion of configuration under catalytic conditions. Chemoselectivity in bismesylates was observed in favour of the secondary mesylate. Additionally, based on the experimental results, a possible catalytic cycle for the halogenation has been proposed.
- Ortega, Nuria,Feher-Voelger, Andres,Brovetto, Margarita,Padron, Juan I.,Martin, Victor S.,Martin, Tomas
-
supporting information; experimental part
p. 963 - 972
(2011/06/20)
-
- Synthesis of isatins with a chiral substituent at the nitrogen atom
-
(R)-Ethyl 2-(isatin-1-yl)propanoates 8a-c were prepared from the corresponding (R)-arylalanines by Sandmeyer's method in high yield and good enantioselectivity (up to 99%). The key step of the process is the Mitsunobu reaction.
- Kurkin, Alexander V.,Bernovskaya, Anna A.,Yurovskaya, Marina A.
-
experimental part
p. 1500 - 1505
(2009/12/01)
-
- Titanium mediated asymmetric aldol reaction with α-fluoropropionimide enolates
-
Aldol reaction utilising Evans N-(α-fluoropropyl)-2-oxazolidinones with TiCl4 have been explored. Reactions of N-(α-fluoropropyl)-2-oxazolidinones with aliphatic aldehydes generated α-fluoro-β-hydroxy-aldol products with high diastereoselectivi
- Brunet, Vincent A.,O'Hagan, David,Slawin, Alexandra M.Z.
-
p. 1271 - 1279
(2008/02/08)
-
- A new method for stereocontrolled synthesis of substituted tetrahydrothiophenes
-
A variety of substituted 3-acyltetrahydrothiophenes can be prepared with high stereoselectivity in 50-70% yield by acid-promoted condensation of mercapto allylic alcohols 1 (X = S) with aldehydes and ketones. The mercapto allylic alcohol must be substitut
- Ponce, Andres Molina,Overman, Larry E.
-
p. 8672 - 8676
(2007/10/03)
-
- Friedel-Crafts alkylation of aromatic compounds with optically active 2-(mesyloxy)propionates. Synthesis of the optically active anti-inflammatory agent (S)-2-(4-isobutylphenyl)propionic acid
-
Alkylation of benzene, toluene and isobutylbenzene with (S)-2-mesyloxypropanoate substrates 2a-g in the presence of aluminium chloride, affords the corresponding (S)-methyl-2-phenylpropionates in good chemical yields under ultrasound mediated conditions.This method leads to the synthesis of (S)-brufen in 50percent yield within 2 hours at 40 deg C compared with only 17percent under conventional conditions when isobutylbenzene was treated with 2b, thus leading to a significant improvement in selectivity for (S)-ibuprofen (40percent to 59percent).
- Garot, C.,Javed, T.,Mason, T. J.,Turner, J. L.,Cooper, J. W.
-
p. 755 - 758
(2007/10/03)
-
- Molecular properties of the WB4101 enantiomers and of its chiral methyl derivatives for α1-adrenoceptor recognition
-
The optical isomers of the well known α1-antagonist WB4101 and of its derivatives with a methyl group in the oxyethyl moiety were prepared for the evaluation of their α-adrenoceptors binding affinity. By means of a detailed computational analysis, the present work shows that the introduction of a methyl group affects the behaviour of WB4101 in different ways. A limitation of the conformational freedom in certain regions of the torsional subspace of the potential energy function, differences in the reactivity of the protonated species towards a model proton acceptor and the quality of the superposition with the rigid template for α1 antagonists, corynanthine, are examined and discussed in order to select a candidate bioactive form and possible features which act as modulators of the recognition process at the α1-adrenoceptors.
- Villa,Valoti,Villa,Pallavicini,Ferri,Iuliano,Brunello
-
p. 587 - 606
(2007/10/02)
-
- Antiphlogistic aryloxypropionic acids: Configurational study
-
Configurational relationships of a series of antiphlogistic 2-aryloxypropionyl derivatives by means of 1H-NMR and HPLC methods were demonstrated. NMR spectra of racemic mixtures and optically active esters were recorded by adding suitable quant
- Azzolina,Ghislandi
-
p. 713 - 724
(2007/10/02)
-
- Preparation of enantiomerically pure sulfoxides from lactic acid and 3-hydroxybutyric acid. Isopropenyl tolyl sulfoxide and 2-(phenylsulfinyl)acrylate
-
The EPC-synthesis of sulfoxides from readily available starting materials ('chiral pool') is demonstrated for the first time. Cyclic and open-chain thioethers derived from lactic and 3-hydroxybutyric acid are oxidized to sulfoxides, and the resulting prod
- Breitschuh,Seebach
-
p. 1170 - 1178
(2007/10/02)
-
- Preparation of amino acid derivatives
-
A hydroxy-carboxylate ester is converted to an amino-acid-amide by replacement of the --OH group with --N3, via, e.g., CH3 SO2 Cl and NaN3 ; reacting with amine to convert the ester to amide; and hydrogenating --N3 to --NH2. The present process alleviates the conventional use of blocking-deblocking procedures.
- -
-
-
- Hydroxyacetic acid derivatives for the treatment of diabetic complications
-
Racemic and chiral (2R,4R)-4-c-hydroxy-2-4-(substituted)chroman(and thiochroman)-4-acetic acids and their pharmaceutically acceptable salts, their use in the treatment of diabetic complications and intermediates therefor.
- -
-
-
- Preparation of Methyl 2-Arylpropanoates by the Reaction of 2-Hydroxypropiophenone Dimethyl Acetals with Sulfuryl Chloride in the Presence of an Amide or a Weak Base
-
Treatment of 2-hydroxypropiophenone dimethyl acetals (1; R=H, i-Bu, OMe, Ph, Br) with sulfuryl chloride in the presence of an amide or a weak base affords methyl 2-arylpropanoates (2) in good to excellent yields via 1,2-aryl migration of 1.The hydrolysis of 2 leads to the corresponding acids some of which are pharmaceutically important compounds having nonsteroidal anti-inflammatory and analgesic acivities.The aryl migration proceeds stereospecifically with complete inversion of configuration at the β-carbon atom.
- Yamauchi, Takayoshi,Hattori, Kaneaki,Nakao, Kenji,Tamaki, Kentaro
-
p. 4015 - 4018
(2007/10/02)
-
- Preparation of α-arylalkanoic acids
-
Pharmaceutically useful optically active α-arylalkanoic acids or esters, ortho esters, or amides thereof are stereoselectively prepared by contacting an aryl magnesium Grignard reagent with an optically active α-substituted acyl halide to form the optically active aryl α-substituted alkyl ketone, which is ketalized and rearranged to the desired optically active α-arylalkanoic acid or the corresponding ester, ortho ester or amide. In an alternate embodiment, the aryl α-substituted alkyl ketone is reduced to the corresponding alkanol, which is rearranged to the α-arylalkanal. The alkanal so produced is converted to the desired optically active α-arylalkanoic acid by conventional methods.
- -
-
-
- Allylic Selenides in Organic Synthesis: New Methods for the Synthesis of Allylic Amines
-
Oxidative rearrangement of allylic selenides in the presence of various amine nucleophiles provides synthetic access to a variety of allylic amine derivatives.The stereochemical outcome of these reactions has been investigated, and is consistent with a -sigmatropic rearrangement mechanism.Several D-α-amino acids and racemic β,γ-unsaturated α-amino acids were prepared in this manner.A variant of this process employing an achiral allylic selenide and chiral amide afforded protected allylic amines in low diastereoisomeric excess.
- Shea, Regan G.,Fitzner, Jeffrey N.,Fankhauser, John E.,Spaltenstein, Andreas,Carpino, Philip A.,et al.
-
p. 5243 - 5252
(2007/10/02)
-
- Synthesis of (Racemization Prone) Optically Active Thiols by SN2 Substitution Using Cesium Thiocarboxylates
-
The cesium salt of thioacetic acid is prepared by treatment with cesium carbonate.This salt has a solubility of about 0.7 M in DMF (even higher in Me2SO) at 50 deg C.The mesylates of (R)-2-octanol, the ethyl ester and N,N-dimethyl amide of (R)-mandelic acid, (S)-ethyl lactate, (S)-methyl 3-phenyllactate, and (S)-diethyl malate underwent clean SN2 substitution in DMF solution.Racemization occured only in the case of the mesylate of ethyl mandelate when allowed to react in DMF, but complete inversion was achieved on use of absolute ethanol as solvent.Hydrolysis or aminolysis is used to deacylate the thiols (except for aliphatic thioacetates, which are deprotected by treatment with lithium aluminum hydride) to afford 2-mercapto esters or amides.Owing to the sensitivity of mercapto-bearing carbon, some racemization (0-20percent depending on the system) occurs during deprotection.An alternate route to the same materials prepared by the cesium thiocarboxylate method involves treatment of the free alcohol with thioacetic acid in the presence of twofold amount of the preformed salt from diisopropyl azodicarboxylate (DIAD) and triphenylphosphine.This method works well except for ethyl mandelate and N,N-dimethylmandelamide.Scale-up of the reaction is difficult, however, owing to the need for a chromatographic separation.Various NMR methods for determining the enantiomeric excesses of the various products are described.Particularly useful for determination of the high enantiomeric excesses is an internal calibration method based on the use of 13C satellite peaks in the presence of a chiral shift reagent.The enantiomeric excesses of the thiols were determined by conversion to the phosphonodithioates followed by measurement of the meso/d,l ratios obtained from 31P NMR spectra.Attempts to hydrolyze 2-acetylthio esters to the free 2-mercapto carboxylic acids lead to 10-40percent racemization depending on the compound.A partial solution to this problem was found by use of optically pure S bromides obtained from diazotation of (S)-alanine, (S)-phenylalanine, and (S)-valine in the presence of bromide.These bromides, on treatment with cesium thiobenzoate, underwent clean SN2 substitution, and debenzoylation could be brought about without significant racemization
- Strijtveen, Bert,Kellogg, Richard M.
-
p. 3664 - 3671
(2007/10/02)
-
- Asymmetric Carbon to Nitrogen Bond Formation Using Optically Active Allylic Selenides: A New General Method for the Synthesis of N-Protected Optically Active α-Amino Acids
-
Optically active allylic selenides undergo oxidative sigmatropic rearrangement to afford optically active, protected allylic amines.The synthetic utility of this process is demonstrated by the synthesis of several N-protected D-α-amino acids in 78-84percent enantiomeric excess.
- Fitzner, Jeffrey N.,Shea, Regan G.,Fankhauser, John E.,Hopkins, Paul B.
-
p. 417 - 419
(2007/10/02)
-
- 3-Substituted bicyclic azetidinone derivatives
-
Subject of the present invention are compounds of the formula STR1 which can be used as intermediates, wherein R represents hydrogen or Ra, which represents an organic radical bonded to the ring carbon atom via a carbon atom, each of the radicals Rb and Rc represents hydrogen or an organic radical bonded to the ring carbon atom via a carbon atom, it being possible for the two radicals to be bonded to one another, A represents a lower alkylene radical having 2 or 3 carbon atoms between the two hetero atoms, and n represents 0 or 2, the stereoisomers thereof and mixtures of these stereoisomers and also processes for the manufacture of such compounds of the formula I. From compounds of the formula I it is possible to manufacture 6-Ra -2-penem-4-carboxylic acid compounds having antibiotic properties.
- -
-
-
- Results of Process Research. I. Synthesis of O-propionyl>-acetone oxime
-
Efficient and simple procedures for the preparation of O--propionyl>-oxime derivatives 7b-e have been developed.The alkylation of 4-phenol (11) with 7d, the final step of a technical synthesis of 1, has been studied in detail.
- Imfeld, Marquard,Suchy, Milos,Vogt, Peter,Lukac, Teodor,Schlageter, Markus,Widmer, Erich
-
p. 1233 - 1241
(2007/10/02)
-
- Polarimetric Determination of Activation Heat Capacity (ΔCp)
-
The study of reaction mechanisms of solvolytic reactions involves the determination of various kinetic and thermodynamic parameters.To probe solute-solvent interactions, the heat capacity of activation (ΔCp) is sometimes determined.This parameter is a measure of the deviation from linearity of a plot of log k versus 1/T.Hence, the determination of ΔCp) requires very precise kinetic experiments.Most such kinetic experiments are based on conductimetric techniques, which in turn involves salt buffering of the solutions to get precise experimental results.This study is aimed at determining whether salt buffering introduces a systematic bias in the heat capacity of activation.
- Albano, Christer,Wold, Svante
-
p. 357 - 366
(2016/06/15)
-