Glutaric diethyl ester

Biocatalysis plays a central role in the manufacturing of statin side chains (Figure 6.2). A first set of approaches exploits enzymatic desymmetrization reactions, for example, of the methoxyacetyl ester of glutaric acid diethyl ester with commercially available a-chymotrypsin as explored by Ciba SC with a yield of 94% and enantiomeric excess of up to 98% [1]. In the optimized procedure, the substrate was available in a concentration of 1 M at an enzyme/substrate ratio of 7% (wt/wt), and the reaction took approximately a day. The subsequent steps to the final acetonide also involved a pig-liver esterase (PLE) catalyzed selective hydrolysis of the methoxyacetyl group (Figure 6.2a). 

Oxalic esters added in small amounts, with ice-salt cooling, under H2, to Na-ethoxide in ether, then glutaric acid ester added, refluxed 1 hr., the ether distilled off, the mixture heated to 105°, and the resulting Na-compound decomposed in cold 20%-H2SO4 —diethyl cyclopentane-l,2-dione-3,5-dicarboxylate. Y 65 %. (G. Hesse and H. Bucking, A. 563, 31 (1949) f. e. s. G. Hesse and K. W. F. Bockmann, A. 563,37 (1949).)... 

Amino-l-cyclohexylmethylphosphonic acid diethyl ester was utilized for the preparation of hapten 1, recently employed to induce the first monoclonal catalytic antibodies capable of catalyzing peptide bond formation[97]. The key steps of the synthesis of 1 include (a) preparation of scalemic a-aminophosphonate, (b) generation of the p-nitrobenzyl ester, (c) installation of a suitable second phosphonate ester linkage, (d) M-acylation with glutaric anhydride. 

In the collidine class there are possibly two groups, D and E (Fig. 4), capable of induction. The compound containing group E is )S-methyl glutaric acid diethyl ester. The compound containing groups D and E is DDC, a powerful inducer. 

The chiral complex 54, formed from LiAlFLj, (15,2/f)-(+)- or (l/f,2S)-(—)-iV-methyl-ephedrine (1 equiv.) and 3,5-dimethylphenol (2 equiv.) and originally introduced for the reduction of ketones with 15-80% e.e.s, has also been shown to reduce oximes of a-keto esters with good stereoselectivity. Applied to the reduction of diethyl 2-hydroxyimmo[4- " C]glutarate, it provided [4- " C]glutamic acid diethyl ester in >60% yield and 80% e.e. ". ... 

The Michael reaction of nitriles with unsaturated carbonyl compounds was examined using the SA-NEtj catalyst As shown in Table 1.6, the SA-NEtj showed the highest catalytic activity for the Michael reaction of ethyl 2-cyanopropionate with ethyl acrylate to afibrd 2-cyano-2-methyl glutaric acid diethyl ester in 94% yield (entry 1). SiOj-NEtj was much less active under the reaction conditions (entry 2). Neither triethylamine nor sihca-alumina promoted the desired addition reaction (entries 3 and 4). Notably, the reaction scarcely proceeded with the... 

With diethyl malonate. Two different products are obtainable in moderate yield by reaction of malonic ester with formalin. With a 1 2 ratio of aldehyde to ester and diethylamine as catalyst, the product is the tetraester (1), an intermediate in one synthesis of glutaric acid. With a 2 1 ratio and potassium bicarbonate as catalyst, the product is the crystalline solid diethyl bis(hydroxymethyl)malonate (2). ... 

The rates of alkaline hydrolysis of methyl pyridazine-3- and -4-carboxylate were correlated with those of pyridinecarboxylates and benzoates. Diethyl pyridazine-4,5-dicarboxylate (214) reacts with 1,3-diphenylguanidine in the presence of sodium hydride to give the spiro compounds 215, the structure of which was determined by X-ray analysis. Related spiro compounds were obtained from the above ester and esters of glutaric or acetonedicar-boxylic acids. 5-Aminopyridazine-4-carboxylic acid is simply synthesized from the 5-carboxamido analog by Hofmann rearrangement. ... 

The question of regiochemistry does not arise in the case of diesters. Diethyl succinate has been converted to the disilyl ketene acetal (59) in good yield. A number of glutarate esters (60) have been similarly transformed to (61). ... 

Dichlorotoluene Diethyl ether Diethyl ketone Diethylene glycol Diethylene glycol methyl ether Diethylene glycol n-butyl ether Dimethyl esters of adipic, glutaric and succinic acids... 

Cyclic j -diketones from ketocarboxylic acid esters. Diethyl a-methyl-a-acetyl-glutarate in dry ether added dropwise with stirring to a suspension of alcohol-free K-ferf-butoxide in dry ether, and refluxed 3 hrs. -> ethyl l-methyl-2,4-dioxocyclohexane-l-carboxylate. Y 70.4%. S. M. Mukherji, R. K. Sharma, and O. P. Vig, Soc. 1958, 4770. 

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