10488-87-6

Usage

Synthesis Reference(s)

The Journal of Organic Chemistry, 54, p. 4229, 1989 DOI: 10.1021/jo00278a047Tetrahedron Letters, 27, p. 4745, 1986 DOI: 10.1016/S0040-4039(00)85054-6

InChI:InChI=1/C12H14O3/c1-3-15-12(14)9(2)11(13)10-7-5-4-6-8-10/h4-9H,3H2,1-2H3

Upstream product

• 110-89-4 piperidine 
• 60-29-7 diethyl ether 
• 314248-94-7 ethyl 2-bromo-2-methyl-3-oxo-3-phenylpropanoate 
• 872269-25-5 4-methyl-3-phenyl-pentenedioic acid diethyl ester 
• 94-02-0 ethyl 3-oxo-3-phenylpropionate 
• 74-88-4 methyl iodide 
• 141-78-6 ethyl acetate 
• 93-89-0 benzoic acid ethyl ester 
• 4303-71-3 triphenylmethyl sodium 
• 105-37-3 Ethyl propionate 
• 98-88-4 benzoyl chloride 
• 21382-82-1 (carbethoxyethylidene)triphenylphosphorane 
• 74-83-9 methyl bromide 
• 1585-45-1 N-(diphenylmethylene)benzamide 

Downstream Products

• 102005-43-6 2-dimethylaminomethyl-2-methyl-3-oxo-3-phenyl-propionic acid ethyl ester 
• 144205-89-0 ethyl 2-methyl-2-allyl-3-oxo-3-phenylpropanoate 
• 10488-96-7 5-Methyl-2,6-diphenylpyrimidin-4(3H)-one 
• 4987-28-4 2-amino-5-methyl-6-phenylpyrimidin-4(3H)-one 
• 7713-78-2 4-methyl-5-phenyl-1,2-dihydro-3H-pyrazol-3-one 
• 29879-49-0 4-methyl-3-phenyl-2H-isoxazol-5-one 
• 120586-56-3 ethyl pyruvate oxime 
• 24956-48-7 2-methyl-3-oxo-3-phenyl-propionic acid amide 
• 23985-58-2 3-hydroxy-2-methyl-3-phenyl-propionic acid 
• 91552-10-2 3-chloro-2-methyl-3-phenyl-acrylic acid 
• 4767-01-5 2-methyl-3-oxo-3-phenylpropionic acid 
• 20999-77-3 1-phenyl-propane-1,2-dione-2-phenylhydrazone 
• 314248-94-7 ethyl 2-bromo-2-methyl-3-oxo-3-phenylpropanoate 
• 860764-04-1 2-methyl-2-nitroso-3-oxo-3-phenyl-propionic acid ethyl ester 

Relevant academic research and scientific papers

Enantiomerically enriched preparation of enolizable β-keto amides. Diastereoselective α-acylation and subsequent aminolysis of 2-acyl-3-phenyl-l-menthopyrazoles

After deprotonation with LDA, 2-acyl-3-phenyl-l-menthopyrazoles (13) were diastereomerically α-acylated to give N-(3-phenyl-l-menthopyrazolyl) β-keto amides (14-19). The subsequent amides were converted into the corresponding N-alkyl amides (21-24) retain

One-pot multistep mechanochemical synthesis of fluorinated pyrazolones

Solventless mechanochemical synthesis represents a technique with improved sustainability metrics compared to solvent-based processes. Herein, we describe a methodical process to run one solventless reaction directly into another through multistep mechanochemistry, effectively amplifying the solvent savings. The approach has to consider the solid form of the materials and compatibility of any auxiliary used. This has culminated in the development of a two-step, one-jar protocol for heterocycle formation and subsequent fluorination that has been successfully applied across a range of substrates, resulting in 12 difluorinated pyrazolones in moderate to excellent yields.

Structural insights into the desymmetrization of bulky 1,2-dicarbonyls through enzymatic monoreduction

Benzil reductases are dehydrogenases preferentially active on aromatic 1,2-diketones, but the reasons for this peculiar substrate recognition have not yet been clarified. The benzil reductase (KRED1-Pglu) from the non-conventional yeast Pichia glucozyma showed excellent activity and stereoselectivity in the monoreduction of space-demanding aromatic 1,2-dicarbonyls, making this enzyme attractive as biocatalyst in organic chemistry. Structural insights into the stereoselective monoreduction of 1,2-diketones catalyzed by KRED1-Pglu were investigated starting from its 1.77 ? resolution crystal structure, followed by QM and classical calculations; this study allowed for the identification and characterization of the KRED1-Pglu reactive site. Once identified the recognition elements involved in the stereoselective desymmetrization of bulky 1,2-dicarbonyls mediated by KRED1-Pglu, a mechanism was proposed together with an in silico prediction of substrates reactivity.

Radical Chain Reactions of α-Azido-β-keto Esters with Tributyltin Hydride. a Novel Entry to Amides and Lactams through Regiospecific Nitrogen Insertion

A variety of acyclic and carbocyclic α-azido-β-keto esters have been readily prepared from the parent dicarbonyl compounds, and their radical chain reactions with tributyltin hydride have been investigated. These reactions normally result in efficient production of alkoxycarbonyl-substituted amides and lactams and thence provide a new, useful method for regiospecific nitrogen insertion of keto ester compounds. The likely mechanism entails initial addition of tributylstannyl radical to the azido moiety to give a stannylaminyl radical, which readily undergoes intramolecular three-membered cyclization onto the ketone group to form an alkoxyl radical. The alkoxyl radical then undergoes regiospecific β-scission to form a stable ring-opened radical that is eventually reduced by tributyltin hydride to propagate the chain. With certain substrates, concomitant deazidation occurs to an important extent. This process, which is unusually observed in radical reactions of alkyl azides, is ascribed to addition of the stannyl radical to the terminal azido nitrogen; subsequent fragmentation of the ensuing 1,3-triazenyl adduct gives stannyl azide and a deazidated alkyl radical, resonance-stabilized by the adjacent carbonyl groups. The radical reactions of 2-azido-2-(ethoxycarbonyl)-1-tetralone with allyltributylstannane and allyltriphenylstannane have also been investigated with the (missed) aim to achieve nitrogen insertion and concomitant allylation.

Sulfur-Extrusive Rearrangement of α-Acylthio Ester by Lithium Amide

α-Acylthio esters readily undergo facile rearrangement to give β-keto esters on treatment with lithium amide at -78 deg C.Thiolactone 3, a key intermediate for thiolactonic antibiotics, was synthesized by utilizing the rearrangement.

Catalytic asymmetric construction of C-4 alkenyl substituted pyrazolone derivatives bearing multiple stereoelements

An organocatalytic asymmetric process was reported for the sterically precise construction of C-4 alkenyl substituted pyrazolone derivatives bearing multiple stereoelements. A series of interesting products featuring the union of a centrally chiral pyrazolone moiety and an axially chiral styrene unit were obtained in high yield with excellent diastereoselectivity and enantioselectivity (up to 99% ee, >20?:?1 dr). The process has the characteristics of mild reaction conditions, simple operation and broad substrate scope. The result of gram-scale reaction indicates that the reaction has good practicability.

Amide/Ester Cross-Coupling via C-N/C-H Bond Cleavage: Synthesis of β-Ketoesters

Activated primary, secondary, and tertiary amides were coupled with enolizable esters in the presence of LiHMDS to obtain good yields of β-ketoesters at room temperature. Notably, this protocol provides an efficient, mild, and high chemoselectivity method

Synthesis of Dithiolethiones and Identification of Potential Neuroprotective Agents via Activation of Nrf2-Driven Antioxidant Enzymes

Oxidative stress is implicated in the pathogenesis of a wide variety of neurodegenerative disorders, and accordingly, dietary supplement of exogenous antioxidants or/and upregulation of the endogenous antioxidant defense system are promising for therapeutic intervention or chemoprevention of neurodegenerative diseases. Nrf2, a master regulator of the cellular antioxidant machinery, cardinally participates in the transcription of cytoprotective genes against oxidative/electrophilic stresses. Herein, we report the synthesis of 59 structurally diverse dithiolethiones and evaluation of their neuroprotection against 6-hydroxydopamine-or H2O2-induced oxidative damages in PC12 cells, a neuron-like rat pheochromocytoma cell line. Initial screening identified compounds 10 and 11 having low cytotoxicity but conferring remarkable protection on PC12 cells from oxidative-mediated damages. Further studies demonstrated that both compounds upregulated a battery of antioxidant genes as well as corresponding genes' products. Significantly, silence of Nrf2 expression abolishes cytoprotection of 10 and 11, indicating targeting Nrf2 activation is pivotal for their cellular functions. Taken together, the two lead compounds discovered here with potent neuroprotective functions against oxidative stress via Nrf2 activation merit further development as therapeutic or chemopreventive candidates for neurodegenerative disorders.

Complementing Pyridine-2,6-bis(oxazoline) with Cyclometalated N-Heterocyclic Carbene for Asymmetric Ruthenium Catalysis

A strategy for expanding the utility of chiral pyridine-2,6-bis(oxazoline) (pybox) ligands for asymmetric transition metal catalysis is introduced by adding a bidentate ligand to modulate the electronic properties and asymmetric induction. Specifically, a ruthenium(II) pybox fragment is combined with a cyclometalated N-heterocyclic carbene (NHC) ligand to generate catalysts for enantioselective transition metal nitrenoid chemistry, including ring contraction to chiral 2H-azirines (up to 97 % ee with 2000 TON) and enantioselective C(sp3)?H aminations (up to 97 % ee with 50 TON).

Environmentally benign nucleophilic substitution reaction of arylalkyl halides in water using CTAB as the inverse phase transfer catalyst

An environmentally benign, practically scalable and highly selective C-arylalkylation of active methylene compounds is developed using CTAB as the inverse phase transfer catalyst in water. The methodology developed is elaborated into the one-pot synthesis of quinoline derivatives and also applicable to the regioselective N-aralkyl of 2-pyridones.