230642-84-9

Usage

Uses

Used in Pharmaceutical Industry:
4-Vinyl-2,3-dihydrobenzofurane is used as a key intermediate in the synthesis of tasimelteon (T007740) for the treatment of non-24 hour sleep-wake disorder. This condition is often observed in visually impaired patients and is characterized by a misalignment of the circadian rhythm. Tasimelteon, synthesized using 4-vinyl-2,3-dihydrobenzofurane, helps to correct this rhythm disorder, improving sleep patterns and overall quality of life for affected individuals.

InChI:InChI=1/C10H10O/c1-2-8-4-3-5-10-9(8)6-7-11-10/h2-5H,1,6-7H2

Upstream product

• 74-85-1 ethene 
• 774220-36-9 4-bromo-2,3-dihydro-1-benzofuran 
• 90-15-3 α-naphthol 
• 27673-48-9 5,8-dihydro-1-naphthol 
• 36192-01-5 5,8-dihydro-1-naphthyl benzyl ether 
• 45152-58-7 tri-tert-butyl(ethenyl)stannane 
• 289058-20-4 4-chloro-2,3-dihydro-1-benzofuran 
• 199391-75-8 2,3-bis(2-hydroxyethyl)phenol 
• 565197-96-8 4-(2-chloroethyl)-2,3-dihydrobenzofuran 
• 230642-83-8 C₁₇H₁₈O₄S 
• 30595-79-0 2-(2,6-dichlorophenyl)ethan-1-ol 
• 7486-35-3 tri-n-butyl(vinyl)tin 

Downstream Products

• 1205098-82-3 1-(2,3-dihydrobenzofuran-4-yl)ethan-1-one 
• 609799-22-6 [14C]-Tasimelteon 
• 209257-15-8 1-[(1R,2R)-2-(2,3-dihydro-1-benzofuran-4-yl)cyclopropyl]methanamine 
• 209257-15-8 trans-[2-(2,3-dihydro-4-benzofuranyl)cyclopropyl]methanamine 
• 364380-03-0 2-chloro-1-(2,3-dihydrobenzofuran-4-yl)ethane-1-one 
• 209256-42-8 2,3-dihydro-1-benzofuran-4-carbaldehyde 

Relevant academic research and scientific papers

A practical pilot-scale synthesis of 4-vinyl-2,3-dihydrobenzofuran using imidate ester chemistry and phase-transfer catalysis

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%.

Tasimelteon intermediate and preparation method thereof

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.

Gram-Scale Synthesis of Chiral Cyclopropane-Containing Drugs and Drug Precursors with Engineered Myoglobin Catalysts Featuring Complementary Stereoselectivity

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.

Preparation method of 4-vinyl-2,3-dihydrobenzene

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.

A facile and practical synthesis of (-)-tasimelteon

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.

CYCLOPROPYL DIHYDROBENZOFURAN MODULATORS OF MELATONIN RECEPTORS

The present invention relates to new cyclopropyl dihydrobenzofuran modulators of melatonin receptors, pharmaceutical compositions thereof, and methods of use thereof.

SYNTHESIS OF 1-(2,3-DIHYDROBENZOFURAN-4-YL)ETHANONE AS INTERMEDIATE IN THE PREPARATION OF RAMELTEON

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.

PROCESS FOR PRODUCTION OF 4-VINYL-2,3-DIHYDROBENZOFURAN

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.

ACYL GUANIDINE SODIUM/PROTON EXCHANGE INHIBITORS AND METHOD

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.

Process for preparing chiral cyclopropane carboxylic acids and acyl guanidines

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.