Aniline, 3- -, EMME cyclization with

In 1939, Gould and Jacobs reported the condensation of aniline with acetyl malonic ester (AME) and ethoxymethylenemalonate (EMME), respectively, followed by cyclization of anilinomethylenemalonic ester 13 and 14 in mineral oil to afford the esters 15 and 16. Saponification of the esters gave the known acids 17 and 18, respectively. 

A somewhat different approach is used for the preparation of the analogue that contains a trifluoromethyl group. The scheme involves first the conversion of ort/zo-trifluoromethyl aniline (27-1) to a quinolol. The compound is thus condensed with EMME and cyclized thermally (27-2). That intermediate is then saponified the resulting acid is decarboxylated and finally converted to the 4-chloroquinoline (27-3) by reaction with phosphorus oxychloride. The displacement of chlorine with methyl anthranilate (27-4) then affords the coupled intermediate (27-5). An ester interchange of that product with glycerol leads to the glyceryl ester. There is thus obtained the NSAID flocatfenine (27-6) [31]. 

The same scheme affords a true quinolone when applied to an aniline. Condensation of piperonylamine (38-7) with EMME followed by cyclization of... 

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