Malonic acid, ethoxymethylene diethyl ester

Ethoxymethylene malonic acid diethyl ester Diethyl sulfata... 

The starting material may be produced by reacting 6-amino-2-methylthiopyrimidine with ethoxymethylene malonic acid diethyl ester. The intermediate thus produced is converted by boiling in diphenyl ether to 6-ethoxycarbonyl-2-methylthio-5-oxo-5,B-dihydropyrido-[2,3-d]pyrimidine. That is hydrolyzed by sodium hydroxide to cleave the ethoxy group and then ethylated with diethyl sulfate to give the starting material. 

Nit ropheny I) pyridine Ethoxymethylene malonic acid diethyl ester Ethyl iodide Sodium hydroxide... 

The starting material is prepared by reacting 2-amino-6-methylpyridine with ethoxymethylene-malonic acid diethyl ester and then reacting that product with sodium hydroxide. 

MMONTC ACID, DIETHYL ESTER see EMA500 MALONIC ACID, (ETHOXYMETHYLENE)-, DIETHYL ESTER see EEV200... 

ETHYL ETHOXYMETHYLENEMALONATE (Malonic acid, ethoxymethylene-, diethyl ester)... 

From 3(5)-hydroxypyrazoles. 5-Hydroxy-l-phenyl-lH-pyrazole-4-carboxylic acid ethyl ester 303, derived from diethyl (ethoxymethylene)-malonate and phenylhydrazine hydrochloride, when methylated with dimethyl sulfate in aqueous sodium hydroxide solution afforded pyrazole 304 together with pyrazol-3-one 305 in 16% and 33% yield, respectively (95JHC1341) (Scheme 68). 

Equimolar amounts of 4-ethylaniline and diethyl (ethoxymethylene)-malonate were heated together at 120°C for 1 h and then heated under reflux in Dowtherm A to effect cyclization. The resulting crude ester was saponified to give 6-ethyl-4(l//)-quinolone-3-carboxyUc acid in an overall yield of 81%, m.p., (DMF) 257°C (dec.). This acid was decarboxylated in benzophenone at 275°C to give 6-ethyl-4(l//)-quinolone, in a yield of 77%, m.p (H2O) 197.5-198.5°C. 

In one of the Vertex s process approaches, the original synthesis of ester 12 was improved where POCI3 was used to facilitate the Friedel-Crafts acylation. " The conditions to carry out the condensation between aniline and diethyl ethoxymethylene-malonate (10) were similar to those of the discovery route except with somewhat elevated temperature (150 °C vs 110 °C). The greater improvement was to carry out the Friedel-Crafts acylation in the presence of POCI3 and phosphoric acid at 70 °C. The overall yield for converting 10- 12 was 70%, more than doubled the yield for the discovery route. 

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