- Solvent-Directed Epoxide Opening with Primary Amines for the Synthesis of β-Amino Alcohols
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An efficient synthesis of β-amino alcohols from a variety of epoxides and primary unbranched amines in the absence of any catalyst in high yields and regioselectivities is reported. A variety of polar mixed solvent systems allow for the selective formation of secondary amino alcohols over tertiary amino alcohols. The reaction scope extends to a wide variety of aromatic and aliphatic substituted epoxides and primary amines bearing complex functionality.
- Lizza, Joseph R.,Moura-Letts, Gustavo
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supporting information
p. 1231 - 1242
(2017/03/11)
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- Continuous and convergent access to vicinyl amino alcohols
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Five active pharmaceutical ingredients (APIs) containing the vicinyl amino alcohol moiety were synthesized using a convergent chemical assembly system. The continuous system is composed of four flow reaction modules: biphasic oxidation, Corey-Chaykovsky epoxidation, phenol alkylation, and epoxide aminolysis. Judicious choice of reagents and module order allowed for two classes of β-amino alcohols, aryl and aryloxy, to be synthesized in good (27-69%) overall yields.
- Nobuta, Tomoya,Xiao, Guozhi,Ghislieri, Diego,Gilmore, Kerry,Seeberger, Peter H.
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supporting information
p. 15133 - 15136
(2015/10/12)
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- Solvent-free aminolysis of aliphatic and aryloxy epoxides with sulfated zirconia as solid acid catalyst
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Single-step and two-steps synthetic procedure for the synthesis of sulfated zirconia (SZ) was developed, which were calcined at 500, 600 and 700 °C and characterized by various physico-chemical methods such as PXRD, FTIR, surface area, microanalysis, NH3-TPD and DRIFT analysis. These SZ materials were then employed as solid acid catalysts for the aminolysis of different aliphatic/aromatic terminal, aryloxy and meso epoxides with aromatic and aliphatic amines under ambient conditions. Amongst the catalyst prepared, SZ-2-600 prepared in two-steps and 600 ° C calcined was found to be the most efficient catalyst to give p-amino alcohols in up to 98% yield and 7gt;99% regioselectivity. The SZ catalyst was successfully recycled and reused up to six catalytic runs with intact efficiency.
- Shah, Arpan K.,Kumar, Manish,Abdi, Sayed H.R.,Kureshy, Rukhsana I.,Khan, Noor-Ul H.,Bajaj, Hari C.
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p. 105 - 114
(2015/09/28)
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- Magnetic nano Fe3O4 catalyzed solvent-free stereo- and regioselective a-aminolysis of epoxides by amines; A green method for the synthesis of β-amino alcohols
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We report the use of magnetic nano Fe3O4 as a mild heterogeneous catalyst for the aminolysis of epoxides with amines. The approach constitutes a green method for the formation of a variety of β-amino alcohols with very high stereo- and regioselectivity under solvent-free and ambient reaction conditions. The aminolysis of chiral epoxides with amines gave the corresponding chiral β-amino alcohols with complete inversion of stereochemistry. The magnetic nano Fe3O4 catalyst can be easily recovered and recycled. Georg Thieme Verlag Stuttgart New York.
- Kumar, Amit,Parella, Ramarao,Babu, Srinivasarao Arulananda
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p. 835 - 842
(2014/04/17)
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- Fe(OH)3 nano solid material: An efficient catalyst for regioselective ring opening of aryloxy epoxide with amines under solvent free condition
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Iron hydroxide-Fe(OH)3and iron oxides (Fe3O4and Fe2O3) were successfully prepared and characterized. These materials were employed as efficient and environmentally benign heterogeneous catalysts for t
- Shah, Arpan K.,Prathap, K. Jeya,Kumar, Manish,Abdi, Sayed H.R.,Kureshy, Rukhsana I.,Khan, Noor-ul H.,Bajaj, Hari C.
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p. 442 - 450
(2017/02/05)
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- Glycerine and CeClH: An efficient and recyclable reaction medium for ring opening of epoxides with thioamides and amines
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Oxiranes undergo rapid ring-opening reaction with a range of thioamides and amines to afford the corresponding -amino alcohol derivatives. The reactions were carried out using glycerine and cerium(III) chloride as a recyclable reaction medium. All the reactions were carried out at room temperature and the products were obtained in excellent yields. Georg Thieme Verlag Stuttgart New York.
- Narsaiah, A. Venkat,Wadavrao, Sachin B.,Reddy, A. Ramesh,Yadav
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experimental part
p. 485 - 489
(2011/04/16)
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- Bromometric assay of alprenolol and oxprenolol
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Alprenolol (1a) reacts with an excess of bromine to yield the tribromo derivative 3a by addition and monosubstitution, while applying oxprenolol (1b) the disubstituted tetrabromo derivative 2b ist obtained. The N-dealkylated substance 3c was isolated as a by-product. Heating the compounds 2b and 3a with potassium hydroxide in acetone gives the 2-bromoallyl derivatives 5. Using potassium tertbutanolate the 2-propyne 7 is formed from 3a. The different colours, obtained from 1a, 1b, pindolol and propranolol with perchloric acid in acetic acid or conc. sulfuric acid, are suitable for the identification test in the European Pharmacopoeia.
- Goerlitzer,Lorenz
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p. 678 - 682
(2007/10/03)
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- Calcium trifluoromethanesulfonate-catalysed aminolysis of epoxides
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Aminolysis of epoxides catalysed by calcium trifluoromethanesulfonate under mild reaction conditions is described. The novel method is very efficient in the synthesis of wide variety of β-amino alcohols with high regio- and stereoselectivity.
- Cepanec, Ivica,Litvi?, Mladen,Mikulda?, Hrvoje,Bartolin?i?, Anamarija,Vinkovi?, Vladimir
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p. 2435 - 2439
(2007/10/03)
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- Bismuth (III) salts as catalysts in the opening of epoxides by amines
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BiCl3 and Bi (OTf)3 catalyze the opening of epoxides (1-7) by amines (8-12). High regioselectivities are observed. BiCl3 et Bi (OTf)3 catalysent la reaction d'ouverture des epoxydes (1-7) par les amines (8-12). La reaction est fortement regioselective.
- Oussaid, Adyl,Garrigues, Bernard,Oussaid, Boualem,Benyaquad, Fatima
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p. 2315 - 2320
(2007/10/03)
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- Synthesis and bovine β3-adrenergic agonistic activities of a novel series of aryloxypropanolamines
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We synthesized a novel series of 21 aryloxypropanolamine compounds characterized by N-alkyl, aralkyl, and aryl substituents. The compounds showed potent β3-adrenergic agonistic activities in Chinese hamster ovary cells expressing the bovine β3-adrenoceptors with Kact and Ki values of 4.2 ± 3.0 nM and 459 ± 169 nM respectively, for the ligand with the best compromise between potency and affinity. Structure-activity relationships are discussed.
- El Hadri,Nicolle,Guillaume,Leclerc,Pietri-Rouxel,Strosberg,Archimbault
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p. 517 - 522
(2007/10/03)
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- Process for the solid state synthesis of enantiopure B-aminoalcohols from racemic epoxides
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The invention relates to a process for the solid state synthesis of enantiopure β-aminoalcohols by preparing inclusion complexes of aryloxyepoxide with cyclodextrin by adding an epoxide in equimolar ratio in an organic solvent to an aqueous solution of cyclodextrin, reacting the cyclodextrin complex of aryloxyepoxide with a nucleophile in solid state by intimately grinding the mixture using a mortar and pestle, continuing the mixing till the starting epoxide disappeared on tic, removing excess amines under vacuum, extracting the β-aminoalcohols produced with a solvent with yields of more than 50% and enantioselectivity of upto 100%.
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- Determination of the enantiomeric purity and the configuration of β- aminoalcohols using (R)-2-fluorophenylacetic acid (AFPA) and fluorine-19 NMR: Application to β-blockers
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A method has been developed for determining the enantiomeric purity and the absolute configuration of β-aminoalcohols of type ArOCH2CH(OH)CH2NHR (R = iPr, tBu). To determine enantiomeric purity, the amine function was first protected by a benzyl group, then the compound formed was esterified using the acid chloride of (R)-2-fluorophenylacetic acid (AFPA). The 19F NMR analysis of the derivative obtained revealed the presence of two distinctly separate signals (~2.5 ppm), the one for the RS-SR pair being the most deshielded. The configuration was determined directly on the aminoalcohol by using the acid. In stoichiometric conditions, when R = iPr, the amide function was obtained very preponderantly. The 19F NMR spectrum of the amide presented four distinct signals when derivatization was carried out by means of a reaction between the (±)-β-aminoalcohol and the (R)-AFPA. The extreme signals, which were over 3.5 ppm apart, did not belong to the same diastereomer. With R = tBu essentially the ester function was obtained. The first studies revealed the presence of two signals, though not as clearly separated as in the previous cases. Each experiment was simple to perform, and purification was not necessary. Mosher's acid gave unsatisfactory results in each case. (C) 2000 Elsevier Science Ltd.
- Apparu, Marcel,Ben Tiba, Younes,Leo, Pierre-Marc,Hamman, Sylvain,Coulombeau, Christian
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p. 2885 - 2898
(2007/10/03)
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- A new route to amino-2-propanol structures with adrenergic β-blocker activity using low valent titanium
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Amino-2-propanol structures can be obtained by addition to dibenzyl acetals of in situ generated dihalocarbenes using LTV (Low Valent Titanium). This methodology can be used to obtain adrenergic β-blockers with amino-2-propanol structure. Tetrahalomethane are the best dihalocarbene precursors. The yields obtained using halofluromethanes can be increased by addition of carbontetrachloride. A process that can imply halogen transfer may be proposed.
- Bermudez,Del Campo,Sinisterra,Llama
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p. 4137 - 4140
(2007/10/03)
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- Efficient asymmetric hydrogenation of α-amino ketone derivatives. A highly enantioselective synthesis of phenylephrine, levamisole, carnitine and propranolol
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The complexes of pyrrolidine bisphosphine ligands (CPMs) with rhodium (I) were found to be efficient catalysts for asymmetric hydrogenation of α-amino ketone hydrochloride derivatives. Utilizing this methodology, we have developed efficient asymmetric syntheses of the optically active β-amino alcohols, phenylephrine, levamisole, carnitine and propranolol.
- Sukuraba,Takahashi,Takeda,Achiwa
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p. 738 - 747
(2007/10/02)
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- Process for the preparation of arylglycidyl ethers and 3-substituted 1-alkylamino-2-propanols
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A process for the preparation of a pharmaceutically active compound in a stereospecific form of the formula, R1-O-CH2-CHOH-CH2-NH-R2 (I), or a pharmaceutically acceptable salt thereof, like an acid addition salt, and/or a compound in a stereospecific form of the formula wherein R1 is an optionally substituted aryl group including a phenyl or naphthyl group optionally included in a heterocyclic ring system, which is optionally substituted, or is a heteroaromatic 5 or 6 membered ring containing in addition to carbon atoms, one or more atoms selected from nitrogen, sulphur and oxygen, this ring being optionally substituted, and wherein R2 is an alkyl group of 2 to 6 carbon atoms, this alkyl group being optionally substituted, which comprises subjecting a compound of the formula, R1-O-CH2-CH=CH2 (III), to the action of a micro-organism having the ability for stereoselective epoxidation of compound (III) into compound (II), having at least 80% by weight the Sconfiguration, at least partly separating compound (II) and/or reacting compound (II) with a C2-C6 alkylamine group optionally substituted and at least partly separating compound (I) and/or converting compound (I) into the pharmaceutically acceptable salt thereof.
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- Ultra-short-acting β-adrenergic receptor blocking agents. I. (Aryloxy)propanolamines containing esters in the nitrogen substituent
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In an attempt to produce short-acting β-adrenergic receptor blocking agents, we prepared several (aryloxy)propanolamines with ester functions incorporated into the nitrogen substituent. Many of these compounds exhibited a short duration of blocking activity after their continuous intravenous infusion for 40 min. However, their durations were found to increase considerably upon longer intravenous infusion.
- Erhardt,Woo,Gorczynski,Anderson
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p. 1402 - 1407
(2007/10/02)
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- Alteration of relative affinities toward myocardial and vascular β adrenoceptors induced by side-chain substitution of aryloxypropanolamines1
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Several conformationally defined aryloxypropanolamines of the type ArOCH2CH(OH)CH(R)NHR1 have been synthesized and tested in vivo for β-adrenoceptor blockade. Key intermediates in the syntheses were the appropriate cis- and trans-disubstituted olefins. Epoxidation of the olefins, followed by amination of the resulting cis- and trans-epoxides, yielded the desired diastereomeric model compounds with a defined threo and erythro stereochemistry, respectively. All active compounds in this series exhibit a simple, bimolecular, competitive antagonism at β adrenoceptors. Proper substitutions of the alkanolamine side chain result in vascular selective or cardioselective β-adrenoceptor antagonists, probably as a consequence of the sterically altered ability to interact with β1 and β2 adrenoceptors. dl-erythro-1-Phenoxy-3-[3,4-dimethoxyphenethyl)amino] butan-2-ol is a cardioselective β-adrenoceptor antagonist with a selectivity ratio significantly higher than that of practolol (β1/β2>40 vs. β1/β2=22) but of equal potency (pA2 values = 6.66 and 6.64, respectively). Phenyl substitution at C-3 of the alkanolamine side chain drastically reduces affinity to both types of β adrenoceptors (pA25.0), thus representing a cutoff point. It is concluded that steric factors, as manifested by bulk tolerance at various parts of the aryloxypropanolamine side chain, are major determinants of affinity toward β-adrenoceptor subtypes. β-Adrenoceptor blockade is unrelated to the lipophilic character of the test compounds.
- Shtacher,Rubinstein,Somani
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p. 678 - 683
(2007/10/04)
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