Aminomethylenemalonic acid esters

A mixture of o-hydroxyacetophenone, dimethylformamide dimethyl acetal, and abs. xylene heated to 120 bath temp, with distillation of methanol, after ca. 2 hrs. the temp, raised to 150-160 for 0.5 hr., then allowed to stand overnight o-hydroxy-co-dimethylaminomethyleneacetophenone (Y 80%) heated 75 min. at 100 bath temp, with aq. H2SO4 chromone (Y 71%). B. Fohlisch, B. 104, 348 (1971) aminomethylenemalonic acid esters (cf. Synth. Meth. 25, 759) by C-dimethylaminomethylenation s. N. D. Harris, Synthesis 1971, 220. 

Tetrahydroisoquinoline-l-acetic acids from aminomethylenemalonic acid esters s. 12, 540... 

Tetrahydroisoquinoline-l-acetic acids via aminomethylenemalonic acid esters... 

Isopropylidene methoxymethylenemalonate (420) was reacted with amino esters, amino acids, and dipeptides at 95-100°C to give rise to the corresponding isopropylidene aminomethylenemalonates (424) in 54-85% yields (85MI3 86YZ154). 

The thermal ring closure of AM 1 -ethyl-4-oxo-1,4-dihydroquinolin-7-yl)aminomethylenemalonate (605) in diphenyl ether at 260°C for 1 hr afforded l,7-phenanthroline-3,9-dicarboxylic acid 9-ethyl ester (606) in 23% yield (88USP4719302). 

A/-(Furo[3,2-i>]pyridin-2-yl)aminomethylenemalonates (1432) were stirred in a 1.2 N ethanolic solution of potassium hydroxide at ambient temperature for 1.5 hr, or in a 2 N ethanolic solution of sodium hydroxide under reflux for 6 hr, to give the 3-carboxylic acid (1433) in 33-61% yield (84G211). Solutions of N-(furopyridin-2-yI)aminomethylenemalonates (1432) in 2 N hydrochloric acid were refluxed for 2 hr to afford 2-aminofuro-pyridine-3-carboxylates (1434) in 55% and 82 % yields. When the 3-ethoxy-carbonyl derivative (1432, R = Et) was heated in a boiling aqueous ethanolic solution of potassium hydroxide for 2 hr, 2-pyridinylacetic acid (1435) was obtained in 47% yield. The treatment of the 4-nitrophenyl ester of 1432 (R = 4-N02Ph) with ethyl iodide in DMF in the presence of potassium carbonate gave the ethyl ester of 1432 (R = Et) in 91% yield (84G211). 

The hydrolysis of diethyl N-(3-alkoxycarbonyl-2-thienyl)aminomethy-lenemalonates (1439, R = Me, Et) by potassium hydroxide in ethanol yielded diethyl Af-(3-carboxy-2-thienyl)aminomethylenemalonates (1439, R = H) [75GEP2435025, 75JAP(K)77393]. The treatment of the /erf-butyl esters 1439, R = rBu, R1 = R2 = H, Me, (CH2)4] with formic acid or trifluoroacetic acid at room temperature also afforded the carboxylic acid derivatives [1439, R = H, R = R2 = H, Me, (CH2)4] [75JAP(K)77394]. 

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