- Preparation method of tasimelteon intermediate
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The invention provides a preparation method of a tasimelteon intermediate. The preparation method at least comprises the following steps: 1) carrying out a substitution reaction or sulfonation reaction on a compound IV to obtain a compound III; 2) carrying out a reaction on the compound III and hydroxylamine hydrochloride under an alkaline substance condition to obtain a compound II; and 3) performing a reduction reaction on the compound II to obtain a compound I. The method has the advantages of high yield, high purity, few reaction byproducts, simple process operation and low overall cost, and is suitable for industrial production.
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Paragraph 0073; 0076; 0085-0090; 0099-0104; 0113-0118; 0125
(2020/07/15)
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- An efficient and practical asymmetric synthesis of (?)-tasimelteon
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Tasimelteon is a useful drug for the treatment of Non-24 in totally blind individuals. An efficient and convenient asymmetric synthesis of tasimelteon has been developed from 4-vinyl-2,3-dihydrobenzofuran through six steps in 53% overall yield using the Corey–Bakshi–Shibata (CBS0 asymmetric reduction of ketone as a key step.
- Wang, Wenbing,Meng, Xiangwei,Zhu, Jianrong,Zhang, Xingxian
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p. 129 - 135
(2019/01/24)
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- Total synthesis of Tasimelteon
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A simple and efficient approach has been accomplished for the total synthesis of active pharmaceutical ingredient (API) of Tasimelteon which is effective for treatment of non-24-h sleep-wake disorder. Starting from 4-vinyl-2, 3-dihydrobenzofuran, the synthesis involves asymmetric epoxidation, Wittig reaction, reduction of the nitrile group and propionation of the amine. The synthesis was accomplished in four steps in overall 48% yield.
- Li, Xi-An,Yue, Lirong,Zhu, Jianrong,Ren, Huazhong,Zhang, Hong,Hu, Dong-yan,Han, Guangtian,Feng,Nan, Ze-dong
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supporting information
p. 1986 - 1988
(2019/07/03)
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- PROCESS FOR THE PREPARATION OF ENANTIOMERICALLY ENRICHED DIHYDROBENZOFURANS AND INTERMEDIATE COMPOUNDS OBTAINED IN THE PROCESS
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It is described an industrially viable and advantageous process for the preparation of (N- (((1R,2R)-2-(2,3-dihydrobenzofuran-4-yl)cyclopropyl)methyl)propionamide, compound having the formula depicted below and generally known as Tasimelteon, or of intermediates useful in the synthesis thereof: The invention also relates to salts obtained as intermediates of the process.
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- Processes for the Preparation of Tasimelteon and Intermediates Thereof
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The present invention provides processes for the preparation of Tasimelteon (1), as well as processes for the preparation of intermediates of Formulas (2), (3) and (4) useful in the preparation of Tasimelteon (1).
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- Preparation method of tasimelteon
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The invention provides a preparation method of tasimelteon. The preparation method comprises that (S)-4-(oxiranyl-2-yl)-2, 3-dihydrobenzofuran as a starting material undergoes a cyanation reaction to produce (1R, 2R)-2-(2, 3-dihydrobenzofuran-4-yl)cyclopropylcarbonitrile, the (1R, 2R)-2-(2, 3-dihydrobenzofuran-4-yl)cyclopropylcarbonitrile is reduced into ((1R, 2R)-2-(2, 3-dihydrobenzofuran-4-yl)cyclopropyl)methylamine, and the ((1R, 2R)-2-(2, 3-dihydrobenzofuran-4-yl)cyclopropyl)methylamine undergoes an acylation reaction to produce tasimelteon. The method has the advantages of less reaction processes, simple operation, simple after-treatment, high product yield, low raw material cost, industrial production feasibility and large application value.
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Paragraph 0054; 0060; 0068; 0075; 0076; 0078; 0079
(2017/07/19)
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- Synthesis method of 2,3-dihydro-1-benzofuran-4-carbaldehyde
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The invention relates to a synthesis method of 2,3-dihydro-1-benzofuran-4-carbaldehyde. The formula of 2,3-dihydro-1-benzofuran-4-carbaldehyde can be shown in the formula (I). The synthesis method comprises the steps of making a compound shown in the formula (II) be subjected to intramolecular cyclization reaction so as to produce a compound shown in the formula (III) under the existence of alkali metal compounds and Cu(1); making the compound shown in the formula (III) be subjected to reaction together with magnesium and a compound shown in the formula R3CONR1R2(IV) so as to obtain the compound shown in the formula (I). According to the synthesis method of 2,3-dihydro-1-benzofuran-4-carbaldehyde, reaction conditions are mild, procedures are simple, byproducts are few, and thus the synthesis method of 2,3-dihydro-1-benzofuran-4-carbaldehyde is suitable for being applied to large scale industrial production.
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- An optical pure he si Meiqiong preparation method (by machine translation)
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The invention provides a method for synthesis of he si Meiqiong, the synthetic method is: shown in formula I raceme transform - [2 - (2, 3 - dihydro - 4 - benzofuryl) cyclopropyl] methylamine, optically pure splitting agent is soluble in the solvent A, in 0 - 70 °C stirring for 2 - 5 hours, the resulting reaction mixture after treatment shown in formula II (1R, 2R) - [2 - (2, 3 - dihydro - 4 - benzofuryl) cyclopropyl] methylamine; dissolving it in the solvent B, add triethylamine, under the protection of nitrogen into the propionyl chloride, in 25 °C stirring reaction under 1 - 2h, the resulting reaction solution after treatment of formula III shown in optical pure he si Meiqiong. The invention has mild reaction condition, the operation is simple, high yield, low production cost, the quality of the product is good, is suitable for industrial production, and has great practical value and social and economic benefits. (by machine translation)
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Paragraph 0042; 0043; 0044; 0045; 0046; 0047; 0048-0168
(2017/05/16)
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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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- 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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- BENZODIOXOLE, BENZOFURAN, DIHYDROBENZOFURAN, AND BENZODIOXANE MELATONERGIC AGENTS
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Novel derivatives of benzodioxa alkylene ethers are provided which are useful as melatonergic agents.
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