Diethyl acetone-l,3-dicarboxylate

Caviion The reaction of phosphorous pentachloride toith diethyl acetone-l,3-dicarboxylate should be carried out in a hood, since hydrogen chloride is evolved. 

Dimethyl 2,3-pentadienedioate has also been prepared from the enol phosphate of diethyl acetone-l,3-dicarboxylate. ... 

Diethyl acetone-l,3-dicarboxylate (1) reacts with N,N-dimethylforma-mide dimethyl acetal (DMFDMA) in ethanol at room temperature to give diethyl l-dimethylamino-3-oxobut-l-ene-2,4-dicarboxylate (2), which was used without isolation and purification. To this mixture 1 equivalent of a monosubstituted hydrazine was added and then stirred at room temperature or heated under reflux for several hours to form intermediates 3, which were, without isolation, cyclized into 1-substituted 4-ethoxycarbonyl-5-(ethoxycarbonylmethyl)pyrazoles 4 in 24-71% yield (08ACSil019) (Scheme 1). 

Ethyl 2-(4,5-dihydro-5-oxo-lH-p)U azol-3-yl)acetate (5), prepared from diethyl acetone-l,3-dicarboxylate (1) and hydrazine hydrate in ethanol at room temperature, was transformed with DMFDMA in toluene at room temperature into ethyl (Z)-2- 4-[(dimethylamino)methylidene]-4,5-dihy-dro-5-oxo-lH-p5u-azol-3-yl acetate (6) in 76% yield (07H657) (Scheme 2). 

The reaction of l-(2-pyridyl)-3,5-dinitro-2-pyridone 14 with ethyl sodio acetoacetate or diethyl sodio acetone-dicarboxylate gave a mixture of N-(2-pyridyl)nitroacetamide 15, phenol derivatives 16, and a low yield of 2-oxo-2,5-dihydropyrido[1,2-b [ 1,2,4]triazine 4-oxide 17 (79TL1393). The mechanism of the reaction is shown in Scheme 5. 

The amino moiety of the 3-carbohydrazide group of unsaturated and 6,7,8,9-tetrahydro-4-oxo-47/-pyrido[l,2-n]pyrimidine-3-carbohydrazides was condensed with acetone and 5-nitro-2-furoaldehyde (830MR687 88EUP252809). The reaction of 6-methyl-6,7,8,9-tetrahydro-4-oxo-4//-pyrido[l,2-a]pyrimidine-3-carbohydrazide with diethyl 2-[2-dimethyl-amino)vinyl]-6-methylpyridine-3,5-dicarboxylate in boiling ethanol for 4 hours afforded N-( 1,6-naphthyridin-6-yl)-4-oxo-4//-pyrido[ 1,2-a]pyrimi-dine-3-carboxamide 426 (85MIP1). 

Method 6 (best yield) CPB 19,46(1971), JCS 121,1638(1922) To prepare diethylacetone dicarboxylate (1) proceed as in method 3 for cocaine synthesis, substituting 720 ml ethanol for methanol. To 197 g (I), add rapidly with stirring and cooling 208 g PClj, keeping temperature below 50°. When HCl evolution stops, pour into water and add ice as necessary to cool. Extract the red oil with ether and dry, evaporate in vacuum. Boil residue 2 /2 hours with 20% HCl, evaporate the water and dissolve the residue in ether. Dry and evaporate in vacuum to get 100 g 3-CI-giutaconate (II). 100 g (II), 300 g ethanol, 50 ml sulfuric acid and reflux while passing in ethanol vapor until 1.5 L collects. Add water, extract with ether, wash with aqueous Na carbonate and dry, evaporate in vacuum to get 113 g diethyl-3-CI-glutaconate (III). Mix 28 g NaOH, 140 ml water, 10.4 g hydroxylamine.HCl, 280 ml ethanol and cool to -35° in acetone-dry ice bath. Stir and add 30.3 g (111) in 50 ml ethanol over two minutes stir one hour (can let stand twelve hours). Neutralize with... 

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