- Fused-ring nitrogen and sulfur heterocycles by a tandem SN2-Michael addition reaction
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A tandem SN2-Michael addition reaction has been developed for the synthesis of cis- and trans-fused nitrogen and sulfur heterocycles from the cis and trans isomers of ethyl (±)-(2E)-3-[2-(iodomethyl)cyclohexyl]-2-propenoate. Octahydro-1H-isoindole-1-acetic acid and octahydrobenzo[c]thiophene-1-acetic acid derivatives have been prepared and their stereochemistries elucidated using NMR and X-ray crystallographic methods. Cyclization substrates for both the cis- and the trans-fused rings are readily available in four steps from known compounds. Yields for the cyclization range from 80-85% and stereochemical selectivities with respect to the side chain vary from 12.5-16:1 for the cis-fused structures to 6-7.5:1 for the transfused structures. Steric interactions in the transition states for ring closure are proposed to rationalize the observed preferences.
- Bunce, Richard A.,Kotturi, Sharadsrikar V.,Peeples, Christopher J.,Holt, Elizabeth M.
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Read Online
- Method for efficiently synthesizing 1R,2R-cyclohexanedimethanol by gas-solid phase technology
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The invention discloses a method for efficiently synthesizing 1R,2R-cyclohexanedimethanol by a gas-solid phase technology. The method comprises the following steps: continuously inputting a 1R,2R-cyclohexanedicarboxylic acid and/or 1R,2R-cyclohexanedicarboxylic acid derivative solution into a continuous tubular reactor provided with a catalyst in a reducing atmosphere, and performing a continuousreaction at an air speed of 0.01-1000 g/g.h to obtain the 1R,2R-cyclohexanedimethanol. The method fully utilizes the characteristics of the gas-solid phase technology, and raw materials and the product only stay in the reaction system for a short time, so racemization of chiral compounds at a high temperature is effectively prevented, continuous production of 1R,2R-cyclohexanedimethanol is achieved, and the method is suitable for industrial production.
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Paragraph 0062-0073
(2020/01/25)
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- Preparation method for lurasidone hydrochloride
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The invention discloses a preparation method for lurasidone hydrochloride. According to the preparation method, trans-1,2-cyclohexanedicarboxylic acid (SM-1) is used as a raw material and subjected to resolution, methyl esterification, reduction, methylsulfonylation, condensation, recrystallization and salt formation so as to eventually obtain lurasidone hydrochloride. The preparation method provided by the invention greatly reduces production cost and has the characteristics of high product yield, easy operation, low toxicity and suitability for industrial large-scale production.
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Paragraph 0017; 0024; 0031
(2017/08/30)
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- Truncated borrelidin analogues: Synthesis by sequential cross metathesis/olefination for the southern fragment and biological evaluation
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The construction of novel borrelidin analogues is reported in which the northern fragment is truncated to a simple hydroxyundecanecarboxylate and the original cyclopentanecarboxylic acid in the southern fragment is replaced with different six-membered rings. The required precursors were prepared by cross metathesis of the appropriate carbocycle-based homoallylic alcohol with crotonaldehyde followed by HWE olefination of the resulting enal with bromocyanophosphonate. The key aldehyde for intramolecular cross coupling was accessible by oxidation of the hydroxy group of the linked undecanecarboxylate unit. Grignard mediated macrocyclization finally yielded the borrelidin related products. The investigation is complemented by SAR studies and quantum-chemical calculations.
- Gündemir-Durmaz, Tülay,Schmid, Fabian,El Baz, Yana,H?usser, Annette,Schneider, Carmen,Bilitewski, Ursula,Rauhut, Guntram,Garnier, Delphine,Baro, Angelika,Laschat, Sabine
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supporting information
p. 8261 - 8269
(2016/09/09)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF LURASIDONE HYDROCHLORIDE
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Disclosed herein is an improved process for the preparation of Lurasidone and its pharmaceutically acceptable salts via novel intermediate and use thereof for the preparation of an antipsychotic agent useful for the treatment of schizophrenia and bipolar disorder. Further, present invention provides a cost effective and eco-friendly process for producing Lurasidone hydrochloride of formula (I) substantially free of residual solvent(s) at industrial scale.
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- A process for the preparation of intermediates [...] (by machine translation)
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The invention relates to a process for the preparation of intermediates [...], the intermediate body is (3aR, 7aR) - 4 ˊ - (1,2-benzisothiazol-3-yl) eight hydrogen spiral [2H-isoindole -2,1 ˊ-piperazine] a sulfonate. The (1R, 2R) - 1,2-cyclohexane dimethanol as raw materials, dialkyltinacetal after armor is a sulfonic acid ester, with the 3 - (1-piperazinyl) - 1,2 benzothiazin hydrochloride reaction to obtain the required intermediate. (by machine translation)
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Paragraph 0006; 0007
(2017/01/09)
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- Enantioselective Synthesis of ((1 R,2 R)-Cyclohexane-1,2-diyl)bis(methylene)dimethanesulfonate, a Lurasidone Hydrochloride Intermediate
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A concise, economical, and highly enantioselective synthesis of bismesylate intermediate of lurasidone HCl, an antipsychotic, has been developed. The key steps involved in the synthesis are thionyl chloride-catalyzed esterification of tetrahydrophthalic anhydride in MeOH, epimerization of cis to trans isomer, hydrolysis of the diester, resolution of the diacid, reduction with Red-Al, and finally bismesylation of the corresponding diol, which provided the desired intermediate ((1 R,2 R)-cyclohexane-1,2-diyl)bis(methylene) dimethanesulfonate in overall good yield.
- Ravi Ganesh,Pachore, Sharad S.,Pratap,Umesh,Basaveswara Rao,Murthy,Suresh Babu
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p. 2676 - 2682
(2015/12/18)
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- PROCESS FOR THE PREPARATION OF LURASIDONE HYDROCHLORIDE
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Provided herein is a process for the preparation of the antipsychotic agent lurasidone hydrochloride useful for the treatment of schizophrenia.
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Page/Page column 20; 21
(2014/03/26)
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- PROCESS FOR PREPARING BENZISOTHIAZOL-3-YL-PEPERAZIN-L-YL-METHYL-CYCLO HEXYL-METHANISOINDOL-1,3-DIONE AND ITS INTERMEDIATES
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The present invention discloses process for preparing benzisothiazol-3-yl- piperazin-l-yl-methyl-cyclo hexyl-methanisoindol-l,3-dione and intermediates thereof.
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- PROCESS FOR THE PREPARATION OF AN ANTIPSYCHOTIC AGENT
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The present invention provides a process for the preparation of an antipsychotic agent useful for the treatment of schizophrenia.
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Page/Page column 13
(2012/10/18)
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- Enzymes in Organic Synthesis. 24. Preparations of Enantiomerically Pure Chiral Lactones via Stereospecific Horse Liver Alcohol Dehydrogenase Catalyzed Oxidations of Monocyclic Meso Diols
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Preparative-scale horse liver alcohol dehydrogenase catalyzed oxidation of monocyclic meso diols provides a direct and convenient one-step route to a broad range of chiral γ-lactones of value as synthons in asymmetric synthesis.The general applicability of the method is demonstrated by oxidations of cis-1,2-bis(hydroxymethyl) substrates of the cyclohexyl, cyclohexenyl, cyclopentyl, cyclobutyl, cyclopropyl, and dimethylcyclopropyl series.For each diol, oxidation of the hydroxymethyl group attached to the S chiral center occurs exclusively, and the pure γ-lactone products are isolated in high (68-90percent) yields and of 100percent ee.In contrast, the enzyme does not exhibit significant enantiomeric selectivity in its catalysis of oxidations of the corresponding racemic trans diols.The stereospecificities observed, or lack thereof, are as predicted by the active-site model.
- Jakovac, Ignac J.,Goodbrand, H. Bruce,Lok, Kar P.,Jones, J. Bryan
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p. 4659 - 4665
(2007/10/02)
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