- Preparation method of 2, 2-dimethoxyacetaldehyde
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The invention discloses a preparation method of 1, 2-dimethoxyacetaldehyde. Hydroxyacetaldehyde is adopted as a raw material and a methanol raw material, S2O8 /Zn-MCM-41 solid superacid is adopted as a catalyst, the acidity is high and 2, 2-methoxyethanol can be obtained with high selectivity, then 2, 2-methoxyacetaldehyde is obtained under the action of an oxidizing agent, the product is easy to separate, and the purity of dimethoxyacetaldehyde reaches up to 95% or above.
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Paragraph 0026; 0028; 0029; 0031; 0032; 0034; 0035; 0037
(2020/07/21)
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- A two-step process for the synthesis of hydroxytyrosol
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A new process for the synthesis of hydroxytyrosol (3,4-dihy-droxyphenylethanol), the most powerful natural antioxidant currently known, by means of a two-step approach is reported. Catechol is first reacted with 2,2-dimethoxyacetaldehyde in basic aqueous medium to produce the corresponding mandelic derivative with > 90 % conversion of the limiting reactant and about 70 % selectivity to the desired para-hydroxyalkylat-ed compound. Thereafter, the intermediate is hydrogenated to hydroxytyrosol by using a Pd/C catalyst, with total conversion of the mandelic derivative and 68 % selectivity. This two-step process is the first example of a synthetic pathway for hydroxytyrosol that does not involve the use of halogenated components or reduction methodologies that produce stoichiometric waste. It also avoids the complex procedure currently used for hydroxytyrosol purification when it is extracted from wastewa-ter of olive oil production.
- Ziosi, Paolo,Paolucci, Claudio,Santarelli, Francesco,Tabanelli, Tommaso,Passeri, Sauro,Cavani, Fabrizio,Righi, Paolo
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p. 2202 - 2210
(2018/10/20)
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- A atorvastatin sandbank calcium chiral synthesis of intermediates method
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The invention discloses a synthesis method for a chiral intermediate of atorvastatin calcium, and belongs to the technical field of medical intermediate synthesis. The synthesis method is characterized in that according to the process route, not only are dangerous, highly toxic and expensive chemicals such as butyl lithium, editpotassium cyanide and periodic acid in chemical synthesis prevented from being used, but also an ee value of the chiral intermediate is effectively improved due to usage of a mixed chiral catalysts of titanium iso-propylate and S-xenol. According to the synthesis method, the raw materials are low in cost and easy to obtain, the route operation is easy, the repeatability is good, the yield is very high, and the synthesis method is suitable for industrial production.
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Paragraph 0034-0036
(2017/08/24)
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- Synthesis method of rosuvastatin calcium key chiral intermediate
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The invention discloses a synthesis method of a rosuvastatin calcium key chiral intermediate and belongs to the technical field of synthesis of medical intermediates. According to the technical scheme, the method is characterized as the specification. With the adoption of the process route, use of an expensive medicine, namely, ethyl (R)-4-bromo-3-hydroxybutyrate, is avoided, the ee (enantiomeric excess) value of a product is effectively increased due to use of a chiral catalyst, raw materials of the synthesis method are simple and easy to obtain, the route is simple to operate, the repeatability is good, the yield is very high, and the method is suitable for industrial production.
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Paragraph 0040; 0041; 0042
(2016/10/10)
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- Fructose-6-phosphate aldolases as versatile biocatalysts for nitrocyclitol syntheses
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Efficient and stereoselective polyhydroxylated nitrocyclitol syntheses were performed via biocatalysed aldol reactions. The key step was based on a one-pot/one-enzyme cascade reaction process where two reactions occur: aldolase-catalysed aldolisation and spontaneous intramolecular nitroaldolisation. The synthetic methodology was investigated using fructose-6-phosphate aldolase A129S for the synthesis of known nitrocyclitols. Improvements were obtained which involved less steps and increased yields. Several new nitrocyclitols were also prepared using hydroxyacetone (HA) as the donor and FSA wt. From nitrocyclitol stereochemical analyses, the intramolecular nitro-Henry reaction stereoselectivity was dependent on the donor substrate used, HA or dihydroxyacetone (DHA). Whereas DHA provided two stereoisomers, four were obtained using HA.
- Camps Bres, Flora,Guerard-Helaine, Christine,Fernandes, Carlos,Castillo, Jose A.,Lemaire, Marielle
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p. 1175 - 1181
(2013/10/08)
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- Metal-free, mild, nonepimerizing, chemo- and enantio- or diastereoselective N-alkylation of amines by alcohols via oxidation/imine-iminium formation/reductive amination: A pragmatic synthesis of octahydropyrazinopyridoindoles and higher ring analogues
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A mild step and atom-economical nonepimerizing chemo- and enantioselective N-alkylating procedure has been developed via oxidation/imine-iminium formation/reduction cascade using TEMPO-BAIB-HEH-Bronsted acid catalysis in DMPU as solvent and a stoichiometric amount of amine. The optimized conditions were further extended for the nonenzymatic kinetic resolution of the chiral amine thus formed under nonenzymatic in situ hydrogen-transfer conditions using VAPOL-derived phosphoric acid (VAPOL-PA) as the Bronsted acid catalyst. The enantioselective cascade of the presented reaction was successfully utilized in the synthesis of octahydropyrazinopyridoindole and its higher ring analogues.
- Khan, Imran A.,Saxena, Anil K.
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p. 11656 - 11669
(2014/01/06)
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- Process for the separation, by countercurrentwise liquid-liquid extraction, of a glyoxal diacetal from a crude mixture comprising it
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The invention relates to a method for separating a diacetal of the glyoxal of a raw mixture comprising said diacetal of the glyoxal and a monoacetal of the glyoxal, by means of counter-current liquid-liquid extraction.
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Page/Page column 4-5
(2008/06/13)
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- METHOD FOR PROCESSING COMPOSITIONS CONTAINING 1,1,2,2-TETRAMETHOXYETHANE AND GLYOXAL DIMETHYL ACETAL
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Disclosed is a method for processing an aqueous composition containing 1,1,2,2-tetramethoxyethane, glyoxal dimethyl acetal, and methanol by means of distillation. Said method is characterized in that the composition is processed in a partition column so as to form low-boiling, medium-boiling, and high-boiling fractions. A partition is disposed in the longitudinal direction of the partition column such that a common top column area, a common bottom column area, a feeding zone comprising a rectification section and a stripping section, and a removing zone encompassing a stripping section and a rectification section are created. The aqueous composition is delivered to the central area of the feeding zone.
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Page/Page column 17-23, chart 1/2; 2/2
(2008/06/13)
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- Process for the continuous preparation of acetals of alpha,beta-dicarbonyl compounds
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The production of linear and cyclic acetals of formulae (I) and (Ia) respectively comprises reacting alpha ,beta -dicarbonyl compounds (II) of the type R-CO-CO-R' with alcohols (III) of the type ROH or HO-X-OH continuously in countercurrent apparatus: (RO)2CRCR'(OR)2 (I). The production of linear acetals (I) and cyclic acetals (Ia) comprises reacting alpha ,beta -dicarbonyl compounds, selected from glyoxal and higher dialdehydes, diketones and ketoaldehydes with 1-8 carbon (C) alkyl, 3-8 C cycloalkyl, 2-8 C alkenyl, 2-8 C alkynyl and/or 6-18 C aryl groups, with 1-8 C alkanols, 3-8 C cycloalkanols, 2-8 C alkenols, 2-8 C alkynols or diols with a 2-12 C alk(en)ylene chain continuously in a countercurrent apparatus. [Image] R and R' : H, 1-8 C alkyl, 3-8 C cycloalkyl, 2-8 C alkenyl, 2-8 C alkynyl or 6-18 C aryl R : 1-8 C alkyl, 3-8 C cycloalkyl, 2-8 C alkenyl or 2-8 C alkynyl or a chain X; and X : 2-12 C alkylene or 2-12 C alkenylene linking both O atoms of the alpha -C atom and/or both O atoms of the beta -C atom.
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- Process for continuously preparing acetals of alpha, beta-dicarbonyl compounds
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The present invention relates to a process for preparing acetals of α,β-dicarbonyl compounds of the general formula (R″O)2CRCR′(OR″)2 which are obtained by continuous reaction of α,β-dicarbonyl compounds R—CO—CO—R′ with alcohols R″OH or HO—X—OH in countercurrent.
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- A3 adenosine receptor antagonists
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Disclosed are pyridine and dihydropyridine derivatives, pharmaceutical compositions comprising one or more of these derivatives, and a method of selectively blocking an A3adenosine receptor of a mammal by the use of one or more of these derivatives. An example of the pyridine derivative is of the formula (I): wherein R2is ethyl, R3is ethylsulfanyl; R4is ethyl, propyl, or hydroxypropyl; R5is ethyl, propyl, fluoroethyl, or fluoropropyl; and R6is phenyl or fluorophenyl. The derivatives of the present invention can be used for inhibiting binding of ligands to an adenosine receptor. The derivatives also can be used for characterizing an adenosine receptor.
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- Structure-activity relationships and molecular modeling of 3,5-diacyl- 2,4-dialkylpyridine derivatives as selective A3 adenosine receptor antagonists
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The structure-activity relationships of 6-phenyl-1,4-dihydropyridine derivatives as selective antagonists at human A3 adenosine receptors have been explored (Jiang et al. J. Med. Chem. 1997, 39, 4667-4675). In the present study, related pyridine derivatives have been synthesized and tested for affinity at adenosine receptors in radioligand binding assays. K(i) values in the nanomolar range were observed for certain 3,5-diacyl-2,4- dialkyl-6-phenylpyridine derivatives in displacement of [125I]AB-MECA (N6-(4-amino-3-iodobenzyl)-5'-N-methylcarbamoyladenosine) at recombinant human A3 adenosine receptors. Selectivity for A3 adenosine receptors was determined vs radioligand binding at rat brain A1 and A(2A) receptors. Structure-activity relationships at various positions of the pyridine ring (the 3- and 5-acyl substituents and the 2- and 4-alkyl substituents) were probed. A 4-phenylethynyl group did not enhance A3 selectivity of pyridine derivatives, as it did for the 4-substituted dihydropyridines. At the 2-and 4-positions ethyl was favored over methyl. Also, unlike the dihydropyridines, a thioester group at the 3-position was favored over an ester for affinity at A3 adenosine receptors, and a 5-position benzyl ester decreased affinity. Small cycloalkyl groups at the 6-position of 4-phenylethynyl-1,4- dihydropyridines were favorable for high affinity at human A3 adenosine receptors, while in the pyridine series a 6-cyclopentyl group decreased affinity. 5-Ethyl 2,4-diethyl-3-(ethylsulfanylcarbonyl)-6-phenylpyridine-5- carboxylate, 38, was highly potent at human A3 receptors, with a K(i) value of 20 nM. A 4-propyl derivative, 39b, was selective and highly potent at both human and rat A3 receptors, with K(i) values of 18.9 and 113 nM, respectively. A 6-(3-chlorophenyl) derivative, 44, displayed a K(i) value of 7.94 nM at human A3 receptors and selectivity of 5200-fold. Molecular modeling, based on the steric and electrostatic alignment (SEAL) method, defined common pharmacophore elements for pyridine and dihydropyridine structures, e.g., the two ester groups and the 6-phenyl group. Moreover, a relationship between affinity and hydrophobicity was found for the pyridines.
- Li, An-Hu,Moro, Stefano,Melman, Neli,Ji, Xiao-Duo,Jacobson, Kenneth A.
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p. 3186 - 3201
(2007/10/03)
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- Total synthesis of (+)-isolaurepinnacin. Use of acetal-alkene cyclizations to prepare highly functionalized seven-membered cyclic ethers
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The first synthesis of the title compound is described. The synthesis features an acetal-vinylsilane cyclization to stereoselectively form the cis-2,7-disubstituted oxepene ring and introduce Δ4 unsaturation. Starting with (2R,3S)-2,3-epoxypentan-1-ol (16), mixed acetal 10 is formed in five steps and 72% overall yield. Treatment of 10 with excess BC13 in CH2Cl2 at -78 → 0°C promotes cyclization to afford Δ4-oxepene 39 in 90% yield after deprotection of the silyl ether. Elaboration of the (E)-enyne functionality of the six-carbon side chain completes the synthesis of (±)-isolaurepinnacin.
- Berger, Daniel,Overman, Larry E.,Renhowe, Paul A.
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p. 2446 - 2452
(2007/10/03)
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- THE MONOACETALIZATION OF GLYOXAL: A DIRECT SYNTHESIS OF 2,2-DIMETHOXY AND DIETHOXY ETHANALS
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Direct monoacetalization of glyoxal by methanol or ethanol is described.Yields of 50 to 70percent are obtained.
- Sangsari, Farid Hamedi,Chastrette, Francine,Chastrette, Maurice
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p. 1343 - 1348
(2007/10/02)
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- Les dialkoxy-2,2 ethanals, synthons difonctionnels a deux carbones : preparation par acetalisation du glyoxal et quelques applications en synthese
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Known for a long time, 2,2-dialkoxy ethanals had to be prepare by rather tedious indirect pathways since monoacetalization of glyoxal was unknown.We discovered that it is possible to acetalize only one of the glyoxal functions using a great excess of alcohol, in the presence of an active enough catalyst.With careful monitoring of the reaction, 50 to 70 percent yield of monoacetals is obtained.The monoacetal is formed much quicker than the diacetal and the maximum yield is rather quickly obtained; with further elimination of water, diacetalization proceeds at the expense of the monoacetal.Depending on azeotropic compositions and boiling points, one of the following methods is used: 1.General method: 40 percent aqueous glyoxal (1 mol), alcohol (10 mol), catalyst (0.01 to 0.1 equivalent) and solvent are refluxed with azeotropic water extraction.The monitored (GC) reaction is stopped at the most favourable moment. 2.Method without solvent, convenient for unreactive alcohols, such as i-butanol: water is evaporated from glyoxal solution (1 mol); the residue, alcohol (10 mol) and catalyst are refluxed with water azeotropic extraction. 3.Method without solvent and without water azeotropic extraction: dehydrated glyoxal (1 mol) is refluxed with alcohol (10 mol) and catalyst.This method is the most convenient for methanol and ethanol.This sample and inexpensive preparation of 2,2-dialkoxy ethanals prompted us to perform syntheses of difunctional molecules otherwise only tediously accessible, since easily obtained functionalized acetals can be hydrolysed to functionalized aldehydes which constitute interesting synthons.Hydride or catalytic reduction as well as organometallic reactions lead to alcohols, further hydrolysed into 2-hydroxy aldehydes or oxidized to give way finally to α-ketoaldehydes for which this method provides a general synthetic pathway.From the oximes, prepared by classical methods, nitriles and amines can be obtained.Starting directly from the aldahydes, amines may be prepared by hydrogenation in the presence of ammonia or amines.The reaction of 2,2-dialkoxy ethanals with amides provides hydroxy and alkoxy acetal amides.The Cannizzaro reaction was also investigated; the same reactivity is displayed by formaldehyde and glyoxal monoacetals.Other reactions, among which Wittig and Wittig-Horner, are presently being studied in our laboratory.
- Stambouli, Abdelhamid,Hamedi-Sangsari, Farid,Amouroux, Roger,Chastrette, Francine,Blanc, Alain,Mattioda, Georges
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- Process for preparing substituted oxyacetaldehydes and acetals thereof
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A process is described for the preparation of substituted oxyacetaldehydes and acetals thereof according to the reaction sequence: STR1 wherein R1 and R2 are each lower alkyl or R1 and R2, taken together form a lower alkylene group; wherein R3 is alkyl, alkenyl or alkadienyl and X is halogen selected from the group consisting of chlorine and bromine, the reaction (i) being carried out (1) using a "phase transfer agent" and (2) in a two phase system.
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- Process for preparing substituted oxyacetaldehydes and acetals thereof
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A process is described for the preparation of substituted oxyacetaldehydes and acetals thereof according to the reaction sequence: STR1 WHEREIN R1 and R2 are each lower alkyl or R1 and R2, taken together form a lower alkylene group; wherein R3 is alkyl, alkenyl or alkadienyl and X is halogen selected from the group consisting of chlorine and bromine, the reaction (i) being carried out (1) using a "phase transfer agent" and (2) in a two phase system.
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