- A practical pilot-scale synthesis of 4-vinyl-2,3-dihydrobenzofuran using imidate ester chemistry and phase-transfer catalysis
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A two-step telescoped synthesis of 4-vinyl-2,3-dihydrobenzofuran (2) was demonstrated using imidate ester chemistry and phase-transfer catalysis. Treatment of 2,3-bis(2-hydroxyethyl)-phenol (1) with the Vilsmeier reagent resulted in an in situ generation of a bis-imidate intermediate 4, which was converted to 4-(2-chloroethyl)-2,3-dihydrobenzofuran (6) via a sequential ring closure and chloride displacement reactions. Further dehydrohalogenation of 6 using a phase-transfer catalyst provided an excellent, cost-effective method to prepare high quality 4-vinyl-2,3-dihydrobenzofuran (2). The yields for the two-step telescoped process ranged from 83 to 90%.
- Rao, Meena,Yang, Ming,Kuehner, Daniel,Grosso, John,Deshpande, Rajendra P.
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Read Online
- Tasimelteon intermediate and preparation method thereof
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The invention provides a tasimelteon intermediate and a preparation method thereof. The preparation method comprises the following steps: with a compound a as a raw material, reacting the compound a with benzyl bromide so as to obtain a compound I; then subjecting the compound I to a reaction under the action of a combined catalyst consisting of potassium osmate dihydrate, potassium carbonate, potassium ferricyanide, benzyltriethylammonium chloride and methane sulfonamide or a combined catalyst consisting of osmium tetroxide, potassium carbonate, potassium ferricyanide, benzyltriethylammonium chloride and methane sulfonamide so as to obtain a compound II; subjecting the compound II to an oxidation reaction under the action of sodium periodate or lead tetraacetate so as to obtain an intermediate compound III and carrying out a reduction reaction so as to obtain a compound IV; and subjecting the compound IV to a reduction reaction to remove a benzyl protective group so as to obtain a compound V, then reacting the compound V with p-toluene sulfonyl chloride, carrying out hydroxyl protection and then carrying out cyclization under the action of potassium carbonate so as to obtain the tasimelteon intermediate compound VI. The invention provides a novel process for preparation of the tasimelteon intermediate; and the prepared tasimelteon intermediate has good purity and high quality and is applicable to industrial production.
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- Gram-Scale Synthesis of Chiral Cyclopropane-Containing Drugs and Drug Precursors with Engineered Myoglobin Catalysts Featuring Complementary Stereoselectivity
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Engineered hemoproteins have recently emerged as promising systems for promoting asymmetric cyclopropanations, but variants featuring predictable, complementary stereoselectivity in these reactions have remained elusive. In this study, a rationally driven strategy was implemented and applied to engineer myoglobin variants capable of providing access to 1-carboxy-2-aryl-cyclopropanes with high trans-(1R,2R) selectivity and catalytic activity. The stereoselectivity of these cyclopropanation biocatalysts complements that of trans-(1S,2S)-selective variants developed here and previously. In combination with whole-cell biotransformations, these stereocomplementary biocatalysts enabled the multigram synthesis of the chiral cyclopropane core of four drugs (Tranylcypromine, Tasimelteon, Ticagrelor, and a TRPV1 inhibitor) in high yield and with excellent diastereo- and enantioselectivity (98–99.9% de; 96–99.9% ee). These biocatalytic strategies outperform currently available methods to produce these drugs.
- Bajaj, Priyanka,Sreenilayam, Gopeekrishnan,Tyagi, Vikas,Fasan, Rudi
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p. 16110 - 16114
(2016/12/26)
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- Preparation method of 4-vinyl-2,3-dihydrobenzene
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The invention provides a preparation method of 4-vinyl-2,3-dihydrobenzene. The preparation method comprises the following steps that under the alkaline condition, a compound (1) and a sulfonylation reagent take a reaction to obtain a compound (2); in the inert gas atmosphere, the compound (2) takes a reaction under the alkaline condition to obtain a product (3). The route is simple; three steps of reactions including sulphonate hydrolysis, cyclization and elimination of the compound (2) are skillfully completed in one pot, so that the reaction efficiency is greatly improved; the reaction steps are shortened; the operation work procedure is simplified; the high-purity 4-vinyl-2,3-dihydrobenzene (3) is prepared almost at a quantitative yield. The synthesis method has the advantages that the reaction conditions are mild; the operation is simple and convenient; the yield is high; the selectivity is good; the production cost is low; the product quality is good; the method is suitable for industrial production; great practical application values and social economical benefits are realized. The structural formula is shown as the accompanying drawing.
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Paragraph 0061; 0062
(2017/03/08)
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- CYCLOPROPYL DIHYDROBENZOFURAN MODULATORS OF MELATONIN RECEPTORS
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The present invention relates to new cyclopropyl dihydrobenzofuran modulators of melatonin receptors, pharmaceutical compositions thereof, and methods of use thereof.
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Paragraph 00237
(2016/07/27)
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- A facile and practical synthesis of (-)-tasimelteon
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An efficient and practical route for the synthesis of (-)-tasimelteon from 2,3-bis(2-hydroxyethyl)phenol has been developed. The product was prepared in seven steps in overall 16.4% yield using highly stereoselective cyclopropanation reaction of the intermediate as the key step.
- Mi, Senyang,Sun, Xinzhe,Wu, Chaogang,Zhang, Xingxian
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p. 667 - 669
(2016/11/18)
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- PROCESS FOR PRODUCTION OF 4-VINYL-2,3-DIHYDROBENZOFURAN
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A process for production of 4-vinyl-2,3-dihydrobenzofuran, which comprises a step including a reaction of 4-halo-2,3-dihydrobenzofuran with ethylene in the presence of a palladium compound and a base to produce crude 4-vinyl-2,3-dihydrobenzofuran, and a step of supplying the crude 4-vinyl-2,3-dihydrobenzofuran continuously or intermittently to a distillation apparatus to distill 4-vinyl-2,3-dihydrobenzofuran.
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Page/Page column 6
(2010/10/19)
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- SYNTHESIS OF 1-(2,3-DIHYDROBENZOFURAN-4-YL)ETHANONE AS INTERMEDIATE IN THE PREPARATION OF RAMELTEON
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The present invention relates in general to the field of organic chemistry and in particular to the preparation of 1-(2,3-dihydrobenzofuran-4-yl)ethanone, an intermediate in preparation of (S)-N-[2-(1,6,7,8-tetrahydro-2H-indeno-[5,4-b]furan-8-yl)ethyl]propionamide, i.e. ramelteon.
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Page/Page column 16-17
(2010/11/03)
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- ACYL GUANIDINE SODIUM/PROTON EXCHANGE INHIBITORS AND METHOD
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Acyl guanidines are provided which are sodium/proton exchange (NHE) inhibitors which have the structure wherein n is 1 to 5; X is N or C-R5 wherein R5 is H, halo, alkenyl, alkynyl, alkoxy, alkyl, aryl or heteroaryl; and R1, R2, R3 and R4 are as defined herein, and where X is N, R1 is preferably aryl or heteroaryl, and are useful as antianginal and cardioprotective agents. In addition, a method is provided for preventing or treating angina pectoris, cardiac dysfunction, myocardial necrosis, and arrhythmia employing the above acyl guanidines.
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Page/Page column 33
(2010/02/10)
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- Process for preparing chiral cyclopropane carboxylic acids and acyl guanidines
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A process is provided for preparing chiral cyclopropane carboxylic acids, preferably of the structure which are intermediates used in preparing acyl guanidine sodium/proton exchange (NHE) inhibitors.
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- Copper(I)-catalyzed intramolecular cyclization reaction of 2-(2'- chlorophenyl)ethanol to give 2,3-dihydrobenzofuran
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Functionalized 2,3-dihydrobenzofuran can be synthesized in good yield via an intramolecular cyclization of an aryl chloride and a primary alcohol under the catalysis of copper(I) chloride salt. (C) 2000 Elsevier Science Ltd.
- Zhu, Jingyang,Price, Benjamin A.,Zhao, Shannon X.,Skonezny, Paul M.
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p. 4011 - 4014
(2007/10/03)
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