An improved synthesis and some reactions of diethyl 4-oxo-4H-pyran-2,5-dicarboxylate

Abstract

Ethyl 2-(dimethylamino)methylene-3-oxobutanoate Diethyl oxalate 4-Oxo-4H-pyran-2,5-dicarboxylic acid 4-Oxo-1-phenyl-1,4-dihydropyridine-2,5-dicarboxylic acid a b s t r a c tThe reaction of ethyl 2-(dimethylamino)methylene-3-oxobutanoate with diethyl oxalate in the presence of sodium hydride in THF gave diethyl 4-oxo-4H-pyran-2,5-dicarboxylate, from which 4-oxo-4H-pyran-2,5-dicarboxylic and 4-oxo-1-phenyl-1,4-dihydropyridine-2,5-dicarboxylic acids and their derivatives were obtained in good yields.Ó 2013 Elsevier Ltd. All rights reserved.Chelidonic acid, a c-pyrone compound with the structure shown in Figure 1, is a naturally occurring compound that is widely distributed among many plants. 1 It is contained in the rhizomes of Chelidonium majus L. at quite high concentrations, and has multiple pharmacological effects including mild analgesic, antimicrobial, oncostatic, and central nervous system sedation. 2 In addition, chelidonic acid and chelidamic acid were the most potent inhibitors of glutamate decarboxylase from rat brain, 3 and may attenuate allergic reactions by inhibition of caspase-1 activity. 4Unlike well-studied diethyl chelidonate, 5 diethyl 4-oxo-4H-pyran-2,5-dicarboxylate (diethyl isochelidonate), is much less known. Furthermore, none of the isomeric 4-pyrone dicarboxylic acids I-III has been recorded in the literature (Fig. 1). Diethyl isochelidonate was mentioned for the first time in 2012 in the patent literature, c-Pyrone derivatives bearing electron-withdrawing carbonylcontaining substituents at the 2-and 5-positions have, surprisingly, been poorly investigated, probably due to the limited number of methods available for their preparation. 6,7 At the same time, these compounds are an important class of c-pyrones which can serve as the starting materials for the syntheses of a broad range of heterocyclic systems due to the presence of five electrophilic centers in their molecules (the C-2, C-4 and C-6 atoms of the pyrone system, and the carbonyl carbons of the 2-COR and 5-COR 0 groups). The diverse range of properties of these compounds is due to the fact that, being highly reactive geminally activated push-pull alkenes with a good leaving group at the a-and a 0 -carbon atoms, whose role is played by the enolate anion, they acquire the ability to undergo additional transformations related to c-pyrone ring-opening and heterocyclizations.The present Letter describes an improved synthesis of diethyl isochelidonate (1), which consists of the Claisen condensation of ethyl 2-(dimethylamino)methylene-3-oxobutanoate with diethyl oxalate in the presence of sodium hydride. Moreover, the synthesis 0040-4039/$ -see front matter Ó

Identification and Control of Critical Process Impurities: An Improved Process for the Preparation of Dolutegravir Sodium

“…The yields of all of the stages were low to moderate during the initial optimization either due to lower conversion or due to formation of more impurities. The first stage, namely, ring opening of 2 with aminoacetaldehyde dimethyl acetal, proceeded instantaneously to form a mixture of acyclic intermediates, which cyclized to 3 in varying yields and purity depending upon the conditions employed. A preliminary screening of solvents (ester, chlorinated, hydrocarbon, and protic solvents) pointed out that the reaction was efficient in alcoholic solvent, especially methanol (Table S2, Supporting Information).…”

Synthesis of Diketohexenoic Acid Derivatives by Alkenylation of Indoles and Pyrroles with 4-Pyrones

“…All solvents used were dried and distilled by standard procedures. Known pyrones 1 were prepared by literature procedures …”

“…To increase chemical reactivity of the pyrone ring, we decided to introduce additional electron-withdrawing group at the C-5 position. We have chosen to use readily available derivatives of 5-acyl-4-pyrone-2-carboxylic acid because these compounds contain the oxymethylidenediketone core, which exhibits high reactivity with indoles . Also, in previous research, these pyrones were reported to react smoothly with water as well as with primary and secondary amines.…”

“…We have chosen to use readily available derivatives of 5-acyl-4-pyrone-2-carboxylic acid because these compounds contain the oxymethylidenediketone core, which exhibits high reactivity with indoles . Also, in previous research, these pyrones were reported to react smoothly with water as well as with primary and secondary amines. We have focused our attention on the optimization of the reaction conditions for the synthesis of ethyl indolyldiketohexenoate 3a , 5-benzoyl-2-carbethoxy-4-pyrone ( 1a ) and 2-methylindole ( 2a ) (1.2 equiv) have been used as model compounds (see SI).…”

Chelidonic Acid and its Derivates: General Spectrum of Biological Activity and Osteogenic Properties (Review)

“…Особый интерес в области разработки остеогенных средств привлекают так называемые «малые» молекулы с остеогенными свойствами, к которым относится и хелидоновая кислота (ХК), содержащаяся в ряде лекарственных растений, которая обладает различными видами биологической активности, в том числе, и остеогенной [6][7][8][9].…”