Aminomalonate, dimethyl

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. 

Keywords imidate, dimethyl aminomalonate, aldehyde, 1,3-dipolar cycloaddition, 4,5-dihydrooxazol... 

A similar approach was described by Kim et al. <01MI1403> to build the Furstner synthon from the vinylogous amide 9, previously described, and the commercially available dimethyl aminomalonate hydrochloride as building block for pyrrole systems. The cyclocondensation reaction between the vinylogous amide 9 and dimethyl aminomalonate hydrochloride was performed in acetic acid at room temperature to yield the presumed Intermediate 12 via an acid-catalyzed nucleophilic substitution reaction. The mixture was then diluted with additional acetic acid and heated under reflux to facilitate the intramolecular ring closure and the loss of the methoxycarbonyl moiety to produce the desired pyrrole. Formation of lamellarin O dimethyl ether was achieved as in the Furstner approach <95JOC6637>. 

A mixture of dimethyl 2-(l-ethoxyethylidene)aminomalonate 1 (1.0 g, 4.6 mmol) and freshly distilled aldehyde 2 (4.6 mmol) was heated to 70 °C during the appropriate time (monitored by TLC) under magnetic stilling. The reaction mixture was allowed to cool down. After removal of ethanol in vacuo, the crude residue was purified by chromatography on silica gel (60F 254, Merck) with appropriate eluent. Solvent evaporation gave the desired compounds which crystallized on standing. 

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. 

Some preparations are described in Section 1C(1) and additional preparative data are as follows. Aminoacetonitrile with hydroxylamine gave 2,5-bishydroxy-iminopiperazine (92) (465), which was hydrolyzed with dilute hydrochloric acid to the monoxime in contrast, nitrous acid converted the dioxime (92) into piperazine-2,5-dione (465). fV-(Aminoacyl)aminoacetonitrile with hydroxylamine formed 5-hydroxyiminopiperazin-2-one (1619). Reduction of diethyl hydroxy-iminomalonate in ethanol with hydrogen over palladium-charcoal gave diethyl aminomalonate and 3,6-diethoxycarbonylpiperazine-2,5-dione (821) and heating of diethyl A -methylaminomalonate formed 3,6-diethoxycarbonyl-l,4-dimethyl-piperazine-2,5-dione (1620), which with sodium hydride in dioxane followed by treatment with sulfur monochloride gave 3,6-epidithio- (93) and 3,6-epitetrathio-... 

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. 

A soln. of dimethyl isonitrosomalonate in acetic acid ice-cooled, treated with Zn-dust, and after 15 min. phenacetyl chloride added dimethyl phenacetyl-aminomalonate (Y 89%) suspended in methanol, treated dropwise at room temp, during 1 hr. with a soln. of 1 mole of KOH in methanol, stored 14 hrs., cooled to 0°, and cautiously neutralized with coned. HCl monomethyl phen-acetylaminomalonate (Y 83%) stirred in acetic acid, treated dropwise at room temp, with aq. Na-nitrite, and stirring continued for several hrs. at room temp. 

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