Malonic acid mono-ethyl ester

The acyl carbon of readily available amino acids such as alanine can be converted to a ketone moiety by activation of the acid with carbonyl diimidazole (CDI) and then condensation with an enolate, such as the magnesium enolate of malonic acid, mono ethyl ester. In this particular example, N-Boc alanine was converted to 1.206 using this method O Catalytic hydrogenation of the ketone moiety gave the alcohol group in 1.207, and conversion to the chloride and base induced dehydrohalogen-ation gave ethyl 4-(N-Boc amino)pent-2-enoate (7.205). 

CH3.(CH2)2.C(C02.C2H5XC0.N3) mw 198.23 N 21.20% OB to C02 -153.36% ypl oil, expl. Sol in eth and CC14. Prepn is by reacting the K salt, of the half (or mono) ethyl ester of propyl malonic acid with nitrous acid Refs 1) Beil, not found 2) T. Curtius W, Lehmann, Transformation of alkylated malonic acids into a-amino acids. III. Synthesis of cr-aminovaleric acid, propylmalonylazidic acid. . JPraktChem 125, 211-302 (1930) CA 24, 3215(1930)... 

The acid moiety of an amino acid can be activated for acyl substitution rather than converted to an aldehyde for acyl addition. Boc-alanine was converted to an acyl imidazole by reaction with carbonyl diimidazole (CDI see chapter two, section 2.4), and then condensed with the magnesium enolate of the mono ethyl ester of malonic acid to give keto-ester 5.9. Subsequent catalytic hydrogenation of the ketone moiety gave ethyl 3-hydroxy-5-(N-Boc amino)penlanoate, 5.10 Once the o... 

Ethane tetracarboxylic ethyl ester can be regarded as composed of two malonic ester residues, each acting as a mono-alkyl substituent to the other. The two remaining hydrogen atoms therefore still retain acidic properties, and consequently the ester gives with sodium ethoxide a di-sodium derivative. 

The synthesis of the moxifloxacin core (de Souza, 2006 Martel et al., 1997 Seidel et al., 2000) proceeds from a Grohe-Heitzer sequence as described earlier in the chapter. Unlike the traditional Grohe-Heitzer sequence, however, the opening step involved the reaction between acid chloride 101 with the mono potassium salt of malonic acid monoethyl ester (102) in the presence of triethylamine to deliver ketoester 103 (Scheme 4.18). Treatment of 103 with ethyl orthoformate furnished acrylate 104, which reacted with cyclopropyl amine to afford 105. Cyclization of 105 in the presence of sodium fluoride in DMF gave the moxifloxicin core 106. 

The Brown-Walker 1 method has been found to be of excellent service in the electrolysis of the potassium salts of the mono-esters of malonie acid. The formation of the diethyl ester of succinic acid from ethyl potassium malonate has already been mentioned fp. 103). 

Derivatives,—Of the salts of malonic acid only the alkali metal salts are soluble. The esters of malonic acid have been referred to as the most important derivatives. Di-ethyl malonate is a colorless insoluble liquid boiling at 198°. The mono-sodium di-ethyl ester, referred to in the above reactions, forms white glistening crystals. The disodium di-ethyl malonate forms gall-like masses and is easily decom-... 

Reaction XLIV. (b) Condensation of Alkyl and Aryl Halogen Compounds with the Sodio- and other Metallo-derivatives of Ethyl Aceto-acetate and its Homolognes. (A., 186, 214 201, 143 213, 143.)—Like malonic ester, acetoacetic ester contains two 1 3-carbonyl groups with a methylene group in position 2. It is only to be expected then that it yields with metallic sodium or sodium alcoholate sodio-derivatives from which mono- and di-, alkyl and aryl homologues can be obtained by treatment with a suitable halide, including halogen esters. Acetoacetic acid... 

Ethyl cyanoacetate is readily alkylated under the usual conditions employed for the malonic and acetoacetic ester syntheses (methods 299 and 213) to yield mono- and di-substituted cyano acetates. These substances may then be hydrolyzed and decarboxylated to furnish mono-carboxylic acids (method 265). In many instances, it is difficult to avoid the formation of the dialkylated ester, the yields may be low. Sev-... 

From Malonic Ester.—The same constitution is also proven by an interesting synthesis from malonic ester. Mono-sodium di-ethyl malonate reacts with monobrom, or mono-iodo acetic acid, and yields the ester of a tri-carboxy acid which after hydrolysis to the acid loses carbon di-oxide and yields succinic acid. 

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