Methyl aminomalonate

B) Preparation of 7-Chloro-3-Methoxycarbony/-5-Phenyl-2-0xo-2,3-Dihydro-iH-Benzo [fl-1,4-Diazepine (4347 CB) A solution of 9.2 g (0.04 mol) of compound 4356 CB in 20 ml of methanol is added dropwise, in the course of one hour and 30 minutes, to a boiling solution of 9.2 g (0.05 mol) of the hydrochloride of methyl aminomalonate in 30 ml of methanol. When this is completed, heating under reflux is continued for 30 minutes and the product then concentrated to dryness under reduced pressure. The residue is taken up in water and ether, the ethereal layer separated, the product washed with water and dried over sodium sulfate. The solvent is evaporated under reduced pressure. The residue, which consists of the methyl ester, could not be obtained in the crystalline state. It is dissolved in 25 ml of acetic acid, heated under reflux for 15 minutes, the product evaporated to dryness and the residual oil taken up in ether. A colorless solid separates which... 

The joint action of primary or secondary amines (aniline, allylamine, benzylamine, butylmethylamine, iV-mcthylglycine methyl ester etc.) and copper bis(acetylacetonate) on the thiophen ylide 258 leads to dimethyl aminomalonates 259 by a carbene insertion reaction294. 

The stereoselective Michael addition of the anion derived from diethyl acetyl-aminomalonate with chalcone has been found to be most effective under soliddiquid two-phase conditions in the absence of an added solvent [62]. For optimum overall conversion and enantiomeric excess (56% with 60% ee), A-benzyl-V-methyl-... 

A mixture of 2.0 g of l-(2-nitro-3-chlorophenyl)-l,3-butanedione, 1.9 g of diethyl aminomalonate, 1.5 ml of absolute ethyl alcohol and two drops of piperidine was refiuxed for 5 hours. After cooling, the reaction mixture was allowed to stand and then crystals were separated. The crystals were collected by filtration and then dried to obtain 2.5 g of colorless crystals. The crystals were recrystallized from a mixed solvent of benzene and ether to obtain diethyl N-[ 1-methyl-3-(2-nitro-3-chlorophenyl)-3-... 

A solution of 0.8 g of diethyl N-[l-methyl-3-(2-nitro-3-chlorophenyl)-3-oxopropylidene]aminomalonate in 4 ml of absolute tetrahydrofuran was added dropwise with stirring to a solution prepared with 8 ml of absolute ethanol and 100 mg of metallic sodium. After the reaction mixture was refluxed for 4.5 hours, the solvents were distilled off under reduced pressure. The residue was added with an ice-water and the solution was extracted with ether. The extract was washed with water, dried over anhydrous magnesium sulfate, after which ether was distilled off. The residue was recrystallized from benzene to obtain ethyl 3-(2-nitro-3-chlorophenyl)-5-methylpyrrole-2-carboxylate as colorless needles having MP 220°-223°C. 

The Garner group has developed a silver acetate/triphenylphosphine (10mol%) catalyzed one-pot three-component coupling (Scheme 2.20) of aldehydes 72, methyl acrylate (27), and dimethyl-2-aminomalonate (73,2 equiv).39 Notably, both aliphatic and aromatic aldehydes may participate in the reaction and yields up to 95% can be achieved. 

The models of the renin structure indicated that the P2 subsite was narrow at the backbone region, so disubstitution of the P2 a-carbon was not recommended. Subsequent experimental evidence confirmed this prediction. In one particular series, where epimerization of the aminomalonate at the P2 site of inhibitor 4 (Table 1) was a concern [27], the a-methyl deriv-... 

Shaprio described a nonoxidative method for preparing 2-substituted 4-ox-azolecarboxylic acid esters 591 (Scheme 1.161). He prepared the key intermediate, dimethyl amino[(phenylthio)methyl]malonate 588, in three straightforward steps from diethyl aminomalonate hydrochloride. Acylation of 588 gave the A-acyl derivative 589 in excellent yield, which was sequentially chlorinated and cyclized in one pot to afford the 2,4,4,5-tetrasubstituted oxazoline 590. The author noted that anhydrous conditions were required to minimize sulfoxide formation. This was the only product isolated if the chlorination cyclization sequence was carried out in a hydroxylic solvent. 

The sweet taste of aspartic acid dipeptide esters (I) was discovered by chance in 1969 for a-L-aspartyl-L-phenylalanine methyl ester ( Aspartame , NutraSweet ). The corresponding peptide ester of L-aminomalonic acid (II) is also sweet. 

Peptides, Kke amino acids, can taste bitter, sweet, salty or indifferent. Most natural and synthetic oligopeptides have a bitter taste (see Section 2.3.3.2). A sweet taste indicates dipeptides derived from L-aspartic acid (2-91) and others derived from its lower homologue L-aminomalonic acid (2-92). is always a hydrogen atom or a methyl group, substituents are alkyls or aryls and substituents are esterified carboxyl groups (usually methyl esters, but some ethyl, propyl, isopropyl and other esters are also sweet). The best... 

Derivatives of 2-phenylimidazoles 10, 11 of immunestimulating activities that are obtained by addition of aminomalonic acid amide on hydrochloride iminoester at 0 C, and consequent boiling the mixture in methyl alcohol environment are described in patent [22] ... 

The reaction of H"CH0 with Al-acyl protected dialkyl aminomalonates and a-amino-ketones stops at the hydroxymethylation step. This behavior could be exploited for the synthesis of (R,S)-, (R)- and (5)-[3-"C]serine, (/f,5)-[3- C]cysteine and e.p. [1-"C]-chloramphenicol, as illustrated in Figure 5.38. In the [3-"C]serine preparations, saponification and decarboxylation converted the hydroxy["C]methyl derivatives 121 (R = acetyl orp-nitrobenzoyl), generated from H"CH0 and diethyl iV-acylaminomalonate, to racemic Af-acyl[3-"C]serine (122). Optical resolution of 122 with quinine and brucine followed by acid-catalyzed cleavage of the A -acyl groups afforded the enantiomerically pure... 

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