105337-15-3

Upstream product

• 5402-60-8 2,6-dimethylbenzyl chloride 
• 14920-81-1 methyl 2,6-dimethylbenzoate 
• 62285-58-9 2,6-dimethylbenzyl alcohol 
• 54708-14-4 2,6-dimethylphenylacetonitrile 
• 6781-98-2 2,6-dimethyl-1-chlorobenzene 
• 5764-82-9 bromo(2-ethoxy-2-oxoethyl)zinc 
• 100379-00-8 2,6-dimethylbenzene boronic acid 
• 105-36-2 ethyl bromoacetate 
• 576-22-7 2-Bromo-m-xylene 
• 105-53-3 diethyl malonate 
• 64-17-5 ethanol 
• 1160608-86-5 2-(2-methanesulfinyl-2-methylsulfanyl-vinyl)-1,3-dimethyl-benzene 
• 87-62-7 2,6-dimethylaniline 
• 632-46-2 2,6-dimethylbenzoic acid 

Downstream Products

• 94204-40-7 diethyl 2-(2,6-dimethylphenyl)malonate 
• 938-50-1 2-(2,6-dimethylphenyl)acetic acid 

Relevant academic research and scientific papers

Coupling of Reformatsky Reagents with Aryl Chlorides Enabled by Ylide-Functionalized Phosphine Ligands

The coupling of aryl chlorides with Reformatsky reagents is a desirable strategy for the construction of α-aryl esters but has so far been substantially limited in the substrate scope due to many challenges posed by various possible side reactions. This limitation has now been overcome by the tailoring of ylide-functionalized phosphines to fit the requirements of Negishi couplings. Record-setting activities were achieved in palladium-catalyzed arylations of organozinc reagents with aryl electrophiles using a cyclohexyl-YPhos ligand bearing an ortho-tolyl-substituent in the backbone. This highly electron-rich, bulky ligand enables the use of aryl chlorides in room temperature couplings of Reformatsky reagents. The reaction scope covers diversely functionalized arylacetic and arylpropionic acid derivatives. Aryl bromides and chlorides can be converted selectively over triflate electrophiles, which permits consecutive coupling strategies.

Rapid Construction of Tetralin, Chromane, and Indane Motifs via Cyclative C-H/C-H Coupling: Four-Step Total Synthesis of (±)-Russujaponol F

The development of practical C-H/C-H coupling reactions remains a challenging yet appealing synthetic venture because it circumvents the need to prefunctionalize both coupling partners for the generation of C-C bonds. Herein we report a cyclative C(sp3)-H/C(sp2)-H coupling reaction of free aliphatic acids enabled by a cyclopentane-based mono-N-protected β-amino acid ligand. This reaction uses inexpensive sodium percarbonate (Na2CO3·1.5H2O2) as the sole oxidant and generates water as the only byproduct. A range of biologically important scaffolds, including tetralins, chromanes, and indanes, can be easily prepared by this protocol. Finally, the synthetic application of this methodology is demonstrated by the concise total synthesis of (±)-russujaponol F in a four-step sequence starting from readily available phenylacetic acid and pivalic acid through sequential functionalizations of four C-H bonds.

PROCESS FOR PREPARING ARYL- AND HETEROARYLACETIC ACID DERIVATIVES

The invention relates to a process for preparing aryl- and heteroarylacetic acids and derivatives thereof by reaction of aryl or heteroaryl halides with malonic diesters in the presence of a palladium catalyst, of one or more bases and optionally of a phase transfer catalyst. This process enables the preparation of a multitude of functionalized aryl- and heteroarylacetic acids and derivatives thereof, especially also the preparation of arylacetic acids with sterically demanding substituents.

Palladium-catalyzed cross-coupling of sterically demanding boronic acids with α-bromocarbonyl compounds

A catalyst system generated in situ from Pd(dba)2 and tri(o-tolyl)phosphine mediates the coupling of arylboronic acids with alkyl α-bromoacetates under formation of arylacetic acid esters at unprecedented low loadings. The new protocol, which involves potassium fluoride as the base and catalytic amounts of benzyltriethylammonium bromideas a phase transfer catalyst, is uniquely effective for the synthesis of sterically demanding arylacetic acid derivatives. (Figure presented)

Process for Preparing Aryl- and Heteroarylacetic Acid Derivatives

The present invention relates to a novel process for preparing α-arylmethylcarbonyl compound of the formula (III), characterized in that aryl- and heteroarylacetic acids and derivatives thereof of the formula (I) are reacted with α-halomethylcarbonyl compounds of the formula (II) in the presence of a palladium catalyst, of a phosphine ligand, of an inorganic base and of a phase transfer catalyst, optionally using an organic solvent.

Practical synthesis of 2-arylacetic acid esters via palladium-catalyzed dealkoxycarbonylative coupling of malonates with aryl halides

A new palladium-based system was developed that catalyzes the coupling of aryl halides with diethyl malonates in the presence of mild bases. In the course of the reaction, the intermediately formed diethyl arylmalonate is directly converted into the arylacetic acid ester via liberation of carbon dioxide and an alkanol. This cross-coupling/dealkoxycarbonylation process provides an efficient and high-yielding synthetic entry to diversely functionalized arylacetic acid esters. Two complementary protocols were developed, one of which is optimal for electron-rich, the other for electron-poor aryl halides. Both make use of low loadings of palladium(0) bis(dibenzylideneacetone) (0.5 mol%)/tri-tert-butylphosphonium tetrafluoroborate (1.1 mol%) as the catalyst and diethyl malonate as the reaction solvent. The new procedures are particularly effective for sterically hindered substrates. Copyright

Water works: An efficient palladium-catalyzed cross-coupling reaction between boronic acids and bromoacetate with aminophosphine ligand

Water greatly restrained the formation of self-coupling of boronic acids in a palladium-catalyzed cross-coupling reaction between boronic acids and ethyl bromoacetate with an aminophosphine ligand; good to excellent yields of cross-coupling product were obtained.

Imidazolo-, oxazolo-, and thiazolopyrimidine modulators of TRPV1

Certain TRPV1-modulating imidazolo-, oxazolo-, and thiazolopyrimdine compounds are described. The compounds may be used in pharmaceutical compositions and methods for treating disease states, disorders, and conditions mediated by TRPV1 activity, such as pain, arthritis, itch, cough, asthma, or inflammatory bowel disease.

Synthesis of ortho-substituted arylacetic esters and related compounds by means of Sommelet-Hauser rearrangement of sulfur ylides

The rearrangement of a series of dimethylsulfonium α-substituted benzylides, e.g., 8, in ethanol has been examined. The ylides 8a,b generated in situ by treatment of the sulfonium salts 7a,b with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in ethanol at room temperature, afforded the o-(methylthiomethyl)phenylacetic esters 10a,b as a result of the Sommelet-Hauser rearrangement of the tautomeric ylides 9a,b. By contrast, the ylide 14 possessing afuran ring was stable at room temperature, but, on heating in ethanol, gave the rearranged product 15. The ylide 22 stabilized by an acetyl group provided three rearranged products, 23, 24, and 25, in boiling ethanol. Treatment of the sulfonium salts 30a,b with DBU at room temperature afforded the corresponding rearranged products 31a,b. The sulfonium salt 34a prepared from 33a, on treatment with sodium ethoxide, gave the rearranged product 36a, which was then S-methylated and treated with DBU to give the 1,2,3-trisubstituted benzene 37a. This method was applied to the synthesis of the fenoprofen analog 39 from 39 from 33b,c.