6337-33-3

Usage

Uses

Used in Pharmaceutical Industry:
2,3-dihydro-2,2-dimethylbenzofuran is used as a reagent for the preparation of heteroaryl compounds, which are essential in the development of kynurenine-3-monooxygenase (KMO) inhibitors. KMO inhibitors play a crucial role in the treatment of neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, by modulating the kynurenine pathway and reducing the production of neurotoxic metabolites.

Synthesis Reference(s)

Tetrahedron Letters, 34, p. 6939, 1993 DOI: 10.1016/S0040-4039(00)91836-7Synthesis, p. 950, 1984 DOI: 10.1055/s-1984-31033

InChI:InChI=1/C10H12O/c1-10(2)7-8-5-3-4-6-9(8)11-10/h3-6H,7H2,1-2H3

Upstream product

• 5820-22-4 methylallyl phenyl ether 
• 628-13-7 pyridine hydrochloride 
• 20944-88-1 2-(methylallyl)phenol 
• 56568-74-2 8,8-dimethylbicyclo<5.1.0>octa-3,5-dien-2-one 
• 33316-80-2 1-(2-hydroxyphenyl)-2-methyl-2-propanol 
• 6395-29-5 2-(2-methyl-1-propenyl)phenol 
• 78131-81-4 α-i-propyl-2-hydroxybenzylalcohol 
• 35770-74-2 Phenoxymagnesium bromide 
• 78-84-2 isobutyraldehyde 
• 153529-64-7 7-(2'-hydroxy-2'-methylpropyl)-1H-benzotriazol-1-amine 
• 66865-62-1 2-Acetoxymercurymethyl-2-methyl-2,3-dihydrobenzofuran 
• 126495-44-1 1-(2-bromophenyl)-2-methyl-propan-2-ol 
• 142569-52-6 1-(2-iodophenyl)-2-methyl-2-propanol 
• 930-68-7 cyclohexenone 

Downstream Products

• 42327-95-7 2,3-Dihydro-2,2-dimethyl-7-benzofurancarbonsaeure 
• 5337-94-0 5-Bromo-2,2-dimethyl-2,3-dihydrobenzo[b]furan 
• 1232221-50-9 N-(2,2-dimethyl-2,3-dihydro-benzofuran-7-yl-methyl-idene)-N'-(7-morpholin-4-yl-2-phenyl-pyrazolo[1,5-a]pyrimidin-5-yl)hydrazine 
• 38002-88-9 2,3-dihydro-2,2-dimethylbenzofuran-7-carboxaldehyde 

Relevant academic research and scientific papers

Nickel-Catalyzed Hydrodeoxygenation of Aryl Sulfamates with Alcohols as Mild Reducing Agents

The nickel-catalyzed hydrodeoxygenation of aryl sulfamates has been developed with alcohols as mild reductants. A variety of functional groups and heterocycles were tolerated in this reaction system to give the desired products in high yields. In addition, the gram-scale process and stepwise cine-substitution were also achieved with high efficiency.

6,7,8,9-TETRAHYDRO-5H-PYRIDO[2,3-d]AZEPINE DOPAMINE D3 LIGANDS

The present invention provides compounds of Formula (I): and pharmaceutically acceptable salts thereof wherein the variables R1, R2, R3, R4, R5, a and A are as defined herein; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds or salts, and their uses for treating D3-mediated (or D3-associated) disorders including, e.g., substance addiction, substance abuse, schizophrenia (e.g., its cognitive symptoms), cognitive impairment (e.g., cognitive impairment associated with schizophrenia, AD or PD), Parkinson's disease, mania, anxiety, impulse control disorders, sexual disorders and depression.

Dihydrobenzofuran production from catalytic tandem Claisen rearrangement-intramolecular hydroaryloxylation of allyl phenyl ethers in subcritical water

We herein report a mild method for the preparation of dihydrobenzofurans through hydrothermal catalytic tandem Claisen rearrangement-intramolecular hydroaryloxylation of allyl phenyl ethers. This reaction provides a new method for constructing dihydrobenzofurans, a process that is potentially applicable to natural product synthesis. SBA-15, TS-1, HZSM-5 were chosen as catalysts in a hydrothermal reaction medium between 200 and 320 °C. HZSM-5 catalyst showed the highest catalytic activity, and the effects of molar ratio of allyl phenyl ether-water, time, pressure, temperature and catalyst on the Claisen hydroaryloxylation in hydrothermal condition were investigated. The latter two process variables had the greatest influence on the product yields and distribution. A series of allyl phenyl ether derivatives were also treated in hydrothermal condition with HZSM-5 catalyst to offer high yield of corresponding dihydrobenzofurans.

Cine substitution of arenes using the aryl carbamate as a removable directing group

An efficient and controlled means to achieve a rare cine substitution of arenes is reported. The methodology relies on the strategic use of aryl O-carbamates as readily removable directing groups for arene functionalization. The removal of aryl carbamates is achieved by employing an air-stable Ni(II) precatalyst, along with an inexpensive reducing agent, to give synthetically useful yields across a range of substrates. The net cine substitution process offers a new strategy for analogue synthesis, which complements the well-established logic for achieving arene functionalization by ipso substitution.

Pd(II)-catalyzed hydroxyl-directed C-H activation/C-O cyclization: Expedient construction of dihydrobenzofurans

A Pd(II)-catalyzed C-H activation/C-O cyclization reaction directed by a proximate hydroxyl group has been developed. This reaction provides a new method for constructing dihydrobenzofurans, including spirocyclic analogues, a process that is potentially a

Investigation of the mechanism of C(sp3)-H bond cleavage in Pd(0)-catalyzed intramolecular alkane arylation adjacent to amides and sulfonamides

The reactivity of C(sp3)-H bonds adjacent to a nitrogen atom can be tuned to allow intramolecular alkane arylation under Pd(0) catalysis. Diminishing the Lewis basicity of the nitrogen lone pair is crucial for this catalytic activity. A range of N-methylamides and sulfonamides react exclusively at primary C(sp3)-H bonds to afford the products of alkane arylation in good yields. The isolation of a Pd(II) reaction intermediate has enabled an evaluation of the reaction mechanism with a focus on the role of the bases in the C(sp3)-H bond cleaving step. The results of these stoichiometric studies, together with kinetic isotope effect experiments, provide rare experimental support for a concerted metalation-deprotonation (CMD) transition state, which has previously been proposed in alkane C(sp3)-H arylation. Moreover, DFT calculations have uncovered the additional role of the pivalate additive as a promoter of phosphine dissociation from the Pd(II) intermediate, enabling the CMD transition state. Finally, kinetic studies were performed, revealing the reaction rate expression and its relationship with the concentration of pivalate.

Intramolecular palladium-catalyzed alkane C-H arylation from aryl chlorides

The first examples of efficient and general palladium-catalyzed intramolecular C(sp3)-H arylation of (hetero)aryl chlorides, giving rise to a variety of valuable cyclobutarenes, indanes, indolines, dihydrobenzofurans, and indanones, are described. The use of aryl and heteroaryl chlorides significantly improves the scope of C(sp3)-H arylation by facilitating the preparation of reaction substrates. Careful optimization studies have shown that the palladium ligand and the base/solvent combination are crucial to obtaining the desired class of product in high yields. Overall, three sets of reaction conditions employing PtBu3, PCyp3, or PCy3 as the palladium ligand and K 2CO3/DMF or Cs2CO3/pivalic acid/mesitylene as the base/solvent combination allowed five different classes of products to be accessed using this methodology. In total, more than 40 examples of C-H arylation have been performed successfully. When several types of C(sp3)-H bond were present in the substrate, the arylation was found to occur regioselectively at primary C-H bonds vs secondary or tertiary positions. In addition, in the presence of several primary C-H bonds, selectivity trends correlate with the size of the palladacyclic intermediate, with five-membered rings being favored over six- and seven-membered rings. Regio- and diastereoselectivity issues were studied computationally in the prototypal case of indane formation. DFT(B3PW91) calculations demonstrated that C-H activation is the rate-determining step and that the creation of a C-H agostic interaction, increasing the acidity of a geminal C-H bond, is a critical factor for the regiochemistry control.

Microwave activation of alumina and its use as a catalyst in synthetic reactions

Microwave irradiation is a simple and efficient method of activating gamma alumina. Alumina activated in this manner is an excellent medium in which to carry out the Diels-Alder reaction and, in conjunction with additional microwave irradiation, the Claisen rearrangement. Several 2-allylphenols formed in the Claisen rearrangement rapidly undergo ring closure on alumina to form dihydrobenzofurans demonstrating the Br0nsted acidity of the solid.

Copper(I)-catalyzed aryl bromides to form intermolecular and intramolecular carbon-oxygen bonds

(Chemical Equation Presented) A highly efficient Cu-catalyzed C-O bond-forming reaction of alcohol and aryl bromides has been developed. This transformation was realized through the use of copper(I) iodide as a catalyst, 8-hydroxyquinoline as a ligand, and K3PO4 as a base. A variety of functionalized substrates were found to react under these reaction conditions to provide products in good to excellent yields.

High-yielding palladium-catalyzed intramolecular alkane arylation: Reaction development and mechanistic studies

Palladium-catalyzed alkane arylation reactions with aryl halides are described for the preparation of 2,2-dialkyl-dihydrobenzofuran substrates. These reactions occur in excellent yield and very high selectivity for the formation of one sole product arising from a reaction at nearby methyl groups. Mechanistic and computational studies point to the involvement of a concerted, inner-sphere palladation-deprotonation pathway that is enabled by the presence of three-center agostic interactions at the transition state. This mechanism accurately predicts the experimentally observed kinetic isotope effect as well as the site selectivity and should be useful in the design of new reactions and catalysts. Copyright