- CONTINUOUS FLOW PROCESS AND APPARATUS FOR MANUFACTURE OF DL-2-NITRO-1-BUTANOL
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A continuous process(200) for manufacture of dl-2-nitro-1-butanol from 1-nitropropane is disclosed. The process mixes aqueous solution of sodium hydroxide (A) and a solution of 1-nitropropane (B) dissolved in alcohol(203) at a first molar ratio in a first tubular reactor to form a mixture. The mixture is pumped(205) with an aqueous solution of formaldehyde at a second predetermined molar ratio to a second tubular reactor for a second residence time to form a product stream. The product stream is quenched(207) in glacial acetic acid to obtain quench liquor having dl-2-nitro-1-butanol. The first(130) and the second(150) tubular reactors are maintained at a temperature of 35° C or less. The method produces conversion of at least 89% dl-2-nitro-1-butanol with residence time of 30 minutes or less. Apparatus for continuous production of dl-2-nitro-1-butanol from 1-nitropropane is further disclosed. A method of obtaining dl-2-amino-1-butanol by hydrogenation of the dl-2-nitro-1-butanol is further disclosed.
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Paragraph 0035-0040
(2021/02/12)
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- Development of an engineered thermostable amine dehydrogenase for the synthesis of structurally diverse chiral amines
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Amine dehydrogenases (AmDHs) are emerging as a class of attractive biocatalysts for synthesizing chiral amines via asymmetric reductive amination of ketones with inexpensive ammonia as an amino donor. However, the AmDHs developed to date exhibit limited substrate scope. Here, using directed evolution, we engineered a GkAmDH based on a thermostable phenylalanine dehydrogenase from Geobacillus kaustophilus. The newly developed AmDH is able to catalyze reductive amination of a diverse set of ketones and functionalized hydroxy ketones with ammonia or primary amines with up to >99% conversion, thus accessing structurally diverse chiral primary and secondary amines and chiral vicinal amino alcohols, with excellent enantioselectivity (up to >99% ee) and releasing water as the sole by-product.
- Chen, Fei-Fei,Chen, Qi,Liu, Lei,Wang, Dong-Hao,Wang, Zhi-Long,Xu, Jian-He,Zhang, Zhi-Jun,Zheng, Gao-Wei
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p. 2353 - 2358
(2020/05/13)
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- Borohydride reduction stabilizing system and method for reducing ester into alcohol
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The invention provides a borohydride reduction stabilizing system and a method for reducing ester into alcohol. The borohydride reduction stabilizing system comprises a borohydride reducing agent anda stabilizer for stabilizing the borohydride reducing agent, wherein the borohydride reducing agent is sodium borohydride or potassium borohydride, and the stabilizer is an alkali metal salt of alcohol. On the basis of an existing sodium borohydride/potassium reducing agent, an alcohol alkali metal salt (such as sodium alcoholate or potassium alcoholate) is added, and then the sodium borohydride/potassium reducing agent can keep stable and is not decomposed under a heating condition, so that on one hand, reduction activity is maintained in a relatively high state and the situation of excessiveuse is reduced, and on the other hand, generation of hydrogen is reduced and the process risk is reduced.
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Paragraph 0110; 0111; 0112
(2019/09/13)
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- Rapid and Quantitative Profiling of Substrate Specificity of ω-Transaminases for Ketones
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ω-Transaminases (ω-TAs) have gained growing attention owing to their capability for asymmetric synthesis of chiral amines from ketones. Reliable high-throughput activity assay of ω-TAs is essential in carrying out extensive substrate profiling and establishing a robust screening platform. Here we report spectrophotometric and colorimetric methods enabling rapid quantitation of ω-TA activities toward ketones in a 96-well microplate format. The assay methods employ benzylamine, a reactive amino donor for ω-TAs, as a cosubstrate and exploit aldehyde dehydrogenase (ALDH) as a reporter enzyme, leading to formation of benzaldehyde detectable by ALDH owing to concomitant NADH generation. Spectrophotometric substrate profiling of two wild-type ω-TAs of opposite stereoselectivity was carried out at 340 nm with 22 ketones, revealing subtle differences in substrate specificities that were consistent with docking simulation results obtained with cognate amines. Colorimetric readout for naked eye detection of the ω-TA activity was also demonstrated by supplementing the assay mixture with color-developing reagents whose color reaction could be quantified at 580 nm. The colorimetric assay was applied to substrate profiling of an engineered ω-TA for 24 ketones, leading to rapid identification of reactive ketones. The ALDH-based assay is expected to be promising for high-throughput screening of enzyme collections and mutant libraries to fish out the best ω-TA candidate as well as to tailor enzyme properties for efficient amination of a target ketone.
- Han, Sang-Woo,Shin, Jong-Shik
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p. 3287 - 3295
(2019/06/21)
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- NITROGENOUS HETEROCYCLIC COMPOUND, PREPARATION METHOD, INTERMEDIATE, COMPOSITION AND USE
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Disclosed are a nitrogenous heterocyclic compound, intermediates, a preparation method, a composition and use thereof. The nitrogenous heterocyclic compound in the present invention is as shown in formula I. The compound has a high inhibitory activity towards ErbB2 tyrosine kinase and a relatively good inhibitory activity towards human breast cancer BT-474 and human gastric cancer cell NCI-N87 which express ErbB2 at a high level, and at the same time has a relatively weak inhibitory activity towards EGFR kinase. Namely, the compound is a highly selective small-molecule inhibitor targeted at ErbB2, and hence it has a high degree of safety, and can effectively enlarge the safety window in the process of taking the drug.
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Paragraph 0532
(2019/01/17)
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- The hydrolysis of epoxides catalyzed by inorganic ammonium salts in water: Kinetic evidence for hydrogen bond catalysis
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Naturally-occurring inorganic ammonium ions have been recently reported as efficient catalysts for some organic reactions in water, which contributes to the understanding of the chemistry in some natural environments (soils, seawater, atmospheric aerosols, .) and biological systems, and is also potentially interesting for green chemistry as many of their salts are cheap and non-toxic. In this work, the effect of NH4+ ions on the hydrolysis of small epoxides in water was studied kinetically. The presence of NH4+ increased the hydrolysis rate by a factor of 6 to 25 compared to pure water and these catalytic effects were shown not to result from other ions, counter-ions or from acid or base catalysis, general or specific. The small amounts of amino alcohols produced in the reactions were identified as the actual catalysts by obtaining a strong acceleration of the reactions when adding these compounds directly to the epoxides in water. Replacing the amino alcohols by other strong hydrogen-bond donors, such as trifluoroethanol (TFE) or hexafluoroisopropanol (HFIP) gave the same results, demonstrating that the kinetics of these reactions was driven by hydrogen-bond catalysis. Because of the presence of many hydrogen-bond donors in natural environments (for instance amines and hydroxy-containing compounds), hydrogen-bond catalysis is likely to contribute to many reaction rates in these environments.
- Nozière,Fache,Maxut,Fenet,Baudouin,Fine,Ferronato
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p. 1583 - 1590
(2018/02/06)
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- O -Phthalaldehyde catalyzed hydrolysis of organophosphinic amides and other P(O)-NH containing compounds
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Over 50 years ago, Jencks and Gilchrist showed that formaldehyde catalyses the hydrolysis of phosphoramidate through electrophilic activation, induced by covalent attachment to its nitrogen atom. Given our interest in the use of aldehydes as catalysts, this work was revisited to identify a superior catalyst, o-phthalaldehyde, which facilitates hydrolyses of various organophosphorus compounds bearing P(O)-NH subunits under mild conditions. Interestingly, chemoselective hydrolysis of the P(O)-N bonds could be accomplished in the presence of P(O)-OR bonds.
- Li, Bin-Jie,Simard, Ryan D.,Beauchemin, André M.
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supporting information
p. 8667 - 8670
(2017/08/10)
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- Highly efficient and diastereoselective synthesis of 1,3-oxazolidines featuring a palladium-catalyzed cyclization reaction of 2-butene-1,4-diol derivatives and imines
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A palladium-catalyzed protocol for effective synthesis of 1,3-oxazolidines has been reported. This method is featured by the high diastereoselectivity (dr up to >98/2) and using the readily available 2-butene-1,4-diol derivatives and imines as substrates.
- Chen, Dongxu,Chen, Xiaoyi,Du, Taiping,Kong, Lichun,Zhen, Renwei,Zhen, Shaocheng,Wen, Yihang,Zhu, Gangguo
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supporting information; experimental part
p. 5131 - 5133
(2010/11/18)
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- New, convenient methods of synthesis and resolution of 1,2-amino alcohols
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Oximes of α-keto esters are reduced to obtain the corresponding amino alcohols using NaBH4 in combination with I2, CH 3COOH, TiCl4, ZrCl4, COCl2, H 2SO4, and TMS-Cl in 60-85% yields. The racemic phenylglycinol, phenylalaninol, and 2-aminobutanol are resolved using dibenzoyl-L-tartaric acid to obtain enantiomeric samples of >98% ee.
- Periasamy, Mariappan,Sivakumar, Sangarappan,Reddy, Meda Narsi
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p. 1965 - 1967
(2007/10/03)
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- Cardiac tropism radiopharmaceutical products incorporating a nitride complex of a transition metal and having a rapid myocardial clearance
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The present invention relates to cardiac tropism radiopharmaceutical products incorporating a nitride complex os a transition metal and having a rapid myocardial clearance. PAL These complexes are based on the formula: EQU (MN)L1 L2 (I) PAL in which M is a transition metal such as 99m Tc and L1 and L2 comply with the formula: STR1 in which at least one of the R and R' represents a branched alkyl group having one or more ether functions, a tetrahydrofurfuryl or ether group, a tetrahydrofurfuryl or dioxaspiro or dialkoxy piperidino groups.
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- Cytokine potentiator and pharmaceutical formulation for cytokine administration
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A cytokine activity enhancer comprising an ethanolamine derivative of the following general formula (I) or a salt thereof, or comprising it along with cytokine or a cytokine production promoter; and also a medicine for diseases with lowered cytokine activity, comprising, as the active ingredient, the cytokine activity enhancer: STR1 wherein R1 is H, --CH3, --CH2 CH(CH3)OH or --CH2 CH2 OH; R2 is H, --CH3, --CH2 CH3 or --COOH; and R3 is H, --CH3, --CH2 CH3 or --CH2 NH2.
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- INFLUENCE OF SUBSTITUENTS ON THE RATE OF FORMATION OF DICHLORAMINES
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The kinetics of the disproportionation reactions of chloramines in water have been studied at acidic pH.Disproportionation and protonation constants and the coefficients of absorption of dichloramines were calculated.The mechanism of disproportionation is discused.
- Antelo, Juan Manuel,Arce, Florencio,Parajo, Mercedes,Barro, Pilar Rodriguez
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p. 549 - 552
(2007/10/02)
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- Racemization of optically active amino alcohols
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A process for racemization of optically active amino alcohols by subjecting the amino alcohol to hydrogen under moderate temperature and pressure conditions while in contact with Raney cobalt.
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- Reduction of nitroaliphatics via homogeneous catalysis
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A homogeneous catalytic hydrogenation of nitroalcohols to amino alcohols is described in which a solution of nitroalcohol is contacted with hydrogen under low temperatures and in the presence of a soluble complex of an organometallic compound of Rh, Ir, Pt or Pd and an organophosphine.
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- HOMOGENEOUS HYDROGENATION OF NITROALIPHATIC COMPOUNDS CATALYZED BY GROUP VIII TRANSITION METAL PHOSPHINE COMPLEXES
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A variety of Group VIII transition metal phosphine complexes were shown to be active catalysts for hydrogenation of nitroaliphatic compounds.The catalysis was determined to be homogeneous based on results of selective catalyst poisoning experiments using dibenzocyclooctatetraene and Hg.A deuterium labeling study showed that in the absence of added base the primary hydrogenation pathway does not involve intermediates containing C=N bonds.
- Harsy, Stephen G.
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p. 7403 - 7412
(2007/10/02)
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- Process for delaying the formation and/or reducing the agglomeration tendency of hydrates
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The invention concerns a process for delaying the formation and/or reducing the agglomeration tendency of hydrates in conditions under which a hydrate may be formed, these hydrates being formed from water and gas. The process according to the invention wherein, in particular, an additive comprising at least one compound from the group of hydroxycarbylamides of substituted carboxylic acids is used. Application of the process according to the invention to processes using gases and water, which form hydrates between them, in particular in the petroleum or gas industry.
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- 3-Acyl-4-ethyl-2-oxazolones and oxazolidinones
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This invention relates to the preparation of optically active d-2-aminobutanol by catalytic asymmetric reduction of appropriate dehydro precursors to produce selectively the desired isomer. The same substrates can also be used to prepare the dl-mixture using optically inactive catalysts. The novel substituted-4-ethyl-4-oxazolin-2-one and substituted-4-ethyl-2-oxazolidinone compounds of this invention are useful as intermediates in the production of the antituberculosis drug ethambutol (Myambutol).
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- Substituted pyridines
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This invention relates to substituted pyridines prepared by reacting aldehydes, amines, lower carboxylic acids such as acetic acid in the presence of oxygen. The N-substituted pyridinium salts formed can be converted to pyridines by thermal dealkylation. The reactions can be summarized by the following equations: STR1
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- Process for production of (+)-2-amino-1-butanol
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A process for producing (+)-2-amino-1-butanol comprising optically resolving an N-acyl-DL-aminobutyric acid using an acylase to obtain L-2-aminobutyric acid and an N-acyl-D-aminobutyric acid which is recycled after racemization, esterifying the L-2-aminobutyric acid to form L-2-aminobutyric acid ester, and reducing the L-2-aminobutyric acid ester to form (+)-2-amino-1-butanol.
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- Process for preparing α-aminoalcohols
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Process for preparing an α-aminoalcohol of formula EQU1 wherein R represents hydrogen or alkyl of from 1 to 5 carbon atoms, which comprises contacting a compound of formula EQU2 wherein R has the same meaning as above, with an alcohol of formula R'-OH wherein R' represents benzyl or the group EQU3 in which R" and R"' are independently selected from hydrogen and alkyl of from 1 to 4 carbon atoms in an organic solvent, in the presence of a basic catalyst, at from about 140° to about 170°C., treating the obtained product of formula EQU4 wherein R and R' have the above meanings, with at least an equimolecular amount of a p-toluene-sulfonyl halide, at from about -5° to about 20°C. in the presence of a tertiary organic nitrogen-containing base and reacting in a closed system the resulting compound of formula EQU5 wherein R and R' are as above defined, with an excess of gaseous ammonia, in the presence of an inert organic solvent, at from about 95° to about 120°C. and recovering the resulting product as its acid addition salt.
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- Synthesis of d-2-amino-1-butanol
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D-2-Amino-1-butanol, for the synthesis of ethambutol hydrochloride, d,d'-2,2'-(ethylenediimino)di-1-butanol dihydrochloride, is produced in high purity and good yields by the reaction of butene-1, a nitrile, preferably an excess of acetonitrile, and chlorine to form N-[1-(chloromethyl)propyl]acetimidoyl chloride which is hydrolyzed to dl-2-amino-1-butanol, which can be isolated as the hydrochloride, or free base, or a mixture, resolved with L(+)- tartaric acid and the d-2-amino-1-butanol reacted with ethylene dichloride and then hydrochloric acid to form ethambutol hydrochloride. A minimum of by-products which are conveniently split out permits the economical synthesis of a pharmaceutical grade product.
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- Synthesis of dl-2-amino-1-butanol
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DL-2-Amino-1-butanol, as the free base or a salt, for resolution to d-2-amino-1-butanol, for the synthesis of ethambutol hydrochloride, d,d'-2,2'-(ethylenediimino)di-1-butanol dihydrochloride, is produced in high purity and good yields by the reaction of butene-1, a nitrile, preferably an excess of acetonitrile, and chlorine to form N-[1-(chloromethyl)propyl]acetimidoyl chloride which is hydrolyzed to dl-2-amino-1-butanol hydrochloride. This can be isolated as the hydrochloride, or free base, or a mixture, resolved with L(+)- tartaric acid and the d-2-amino-1-butanol reacted with ethylene dichloride and then hydrochloric acid to form ethambutol hydrochloride. A minimum of by-products which are conveniently split out permits the economical synthesis of a pharmaceutical grade product.
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- Synthesis of ethambutol
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D-2-Amino-1-butanol, for the synthesis of ethambutol hydrochloride, d,d'-2,2'-(ethylenediimino)di-1-butanol dihydrochloride, is produced in high purity and good yields by the reaction of butene-1, a nitrile, preferably an excess of acetonitrile, and chlorine to form N-[1-(chloromethyl)propyl]acetimidoyl chloride which is hydrolyzed to dl-2-amino-1-butanol, which can be isolated as the hydrochloride, or free base, or a mixture, resolved with L(+)-tartaric acid and the d-2-amino-1-butanol reacted with ethylene dichloride and then hydrochloric acid to form ethambutol hydrochloride. A minimum of by-products which are conveniently split out permits the economical synthesis of a pharmaceutical grade product.
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- Process for manufacturing 2-aminobutanol
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The invention relates to a method of preparation of 2-aminobutanol from readily available raw materials. The method of this invention is based on the reaction between 1.2-epoxybutane or isomeric butylene halogenehydrines with ammonia. The product, isomeric aminobutanols, are, subsequently transformed into 2-ethylaziridine by means of esterification with sulphuric acid followed by treatment with alkali. 2-Ethylaziridine is then submitted to a reaction with aromatic carboxylic acid or with aromatic orthobicarboxylic acid anhydride which produces the corresponding monomeric or polymeric amide, which is transformed into 2-aminobutanol by hydrolysis. The method of this invention is a multistage one but is quite simple and employs aqueous solutions and organic solvents, such as chloroform or benzene, which may be easily recovered.
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- Synthesis of N-[1-(chloromethyl)propyl]acetamide
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N-[1-(Chloromethyl)propyl]acetamide, for the synthesis of ethambutol hydrochloride, d,d'-2,2'-(ethylenediimino)-di-1-butanol dihydrochloride, is produced in high purity and good yields by the reaction of butene-1, a nitrile, preferably an excess of acetonitrile, and chlorine to form N-[1-(chloromethyl)propyl]acetimidoyl chloride which is hydrolyzed to N-[1-(chloromethyl)propyl]acetamide. This may be hydrolyzed further to dl-2-amino-1-butanol, which can be isolated as the hydrochloride, or free base, or a mixture, resolved with L(+)-tartaric acid and the d-2-amino-1-butanol reacted with ethylene dichloride and then hydrochloric acid to form ethambutol hydrochloride.
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