Ethyl trifluoroacetoacetate

CuCl/THF followed by catalytic hydrogenation to give the pyrroloquinoline 134. Nitration of the later gave the 9-nitro derivative 135. Reduction of 135 followed by reaction with ethyl trifluoroacetoacetate gave 136 that upon cyclization gave the tetracyclic compound 137 (98JMC623) (Scheme 26). 

The reduction of ethyl trifluoroacetoacetate by bacterial alcohol dehydrogenases has been reported by Zhang et alP and the product used as an intermediate in the synthesis of Befloxatone as shown in Figure 1.42. 

Substituents in the pyranone ring are derived from the dicarbonyl component and hence variation in the nature of 3- and 4-substituents is relatively easy. Thus, ethyl benzoylacetate gives 4-phenylcoumarins as for instance in a synthesis of dalbergin (357) (76T2407, 8iiJC(B)9l8) and use of ethyl trifluoroacetoacetate leads to 4-trifluoromethylcoumarins. A study of the reaction of the latter with 3-aminophenol identified the optimum conditions for coumarin formation, but noted the simultaneous formation of the two quinoline derivatives (358) and (359) (80JOC2283). 

The activation of the trifluoromethyl substituent is strong enough to allow the 1,3-dipolar reaction to occur with trisubstituted dipolarophiles, provided a second electron-withdrawing substituent is present in the molecule (Table 11). Under similar conditions non-fluorinated analogs are unreactive (entry 3).5-77-80 The cycloaddition with ethyl trifluoroacetoacetate is a striking example (Table 11, entry 2) in this case, the dipolarophile reacts in its enolic form (Z-isomer). 

Ethyl trifluoroacetoacetate (3.0 g. 16.2 mmol) and A-(benzylidene)methylamine. V-oxide (1 2.6 g. 19.4 mmol) were refluxed in toluene for 24 h. After evaporation of the toluene, the crude product was filtered on a silica gel column, and the isoxazolidinc obtained by crystallization from cyclohexane yield 3.36 g (65%) mp 94-96 C. 

Both dipolar and contact contributions are important in glycinate complexes. (166) U(iv) complexes with a-alanine, (167) various amino-acids, (168) ethyl trifluoroacetoacetate, (169) tetrakis-(tetra-ethylammonium)octathiocyanatouranate U(NCS)g(NEt4)4, (170) and -diketones (171, 172) have been examined. In studying the ligand exchange kinetics of the latter complexes (172) the mechanism is considered to involve a ninth coordination site in the U(iv) chelate. 

ETHYL TRIFLUOROACETOACETATE (TFAE) AS A USEFUL BUILDING BLOCK IN HETEROCYCLIC SYNTHESIS... 

Compounds 52 and homologues reacted invariably with 1,4-6w-nucleophiles such as ethylenediamine and 2-aminoethanol at the CF3CO group by forming oxazolidines 62 and imidazolidines 64 (Scheme 61, ref. 62). Similar behaviour was encountered with ethyl trifluoroacetoacetate (ref. 61). 

Begue et al. reported the preparation of substituted 2-trifluoromethylfurans through the iodocyclization of y,5- unsaturated ethyl trifluoroacetoacetate. 

Begue, J.P. Bonnet-Delpon, D. Dogbeavou, R. Ourevitch, M. Trifluoromethylated furans via iodocyclisation of y-unsaturated ethyl trifluoroacetoacetates. J. Chem. Soc., Perkin Trans. 1 1993, 2787-2791. 

Preparation of Polycyclic Compounds.—number of routes to bi- and tri-cyclic heterocycles containing the tetrafluorobenzo-moiety have been described (see pp. 381, 390, 397, 400, and 410, and Schemes 20, 22—26, 29. 34, and 39). Ethyl trifluoroacetoacetate and m-anisidine condmse in the presence of acid to give equal amounts of 5- and 7-methoxy-2-trifluoro-methylquinol-4-ones. 8-(Trifluoromethyl)quino]ine derivatives are reported to have anti-inflammatory and analgesic activity. Reaction of CozfCO) ... 

Liping et al. [68] reported the iodine-catalyzed one-pot multicomponent reaction of ethyl trifluoroacetoacetate, indan-l,3-dione, ammonium acetate, and aromatic aldehyde which gave ethyl-6 -hydroxy-l,3-dioxo-2, 4 -diaryl-6 -(trifluoromethyl)-l,3-dihydrospiro[indene-2,3 -piperidine]-5 -carboxylate derivatives 50 as the major product and 2-trifluoromethyl-2,3,4,5-tetrahydro-l/f-indeno[l,2-b]pyridine derivative 51 as the minor product (Scheme 10.33). 

The Knorr pyrrole synthesis was also employed for the synthesis of 3-trifluoropyrroles [91]. Treatment of ethyl trifluoroacetoacetate 267 with sodium nitrite in acetic acid led to the oxime 268. Refluxing with zinc dust and addition of 1,3-dicarbonyl compounds 269 afforded the 3-trifluoromethylpyrroles 270 in moderate yields. Using more acidic trifluoroacetic acid allowed to lower the reaction temperature to 70 °C [92]. Using a similar approach, the tricarboxylic acid ester 273 was prepared starting from the acetone dicarboxylic acid ester 271 and the fluorinated keto ester 272 [93]. 

Reaction of aniline (304) and ethyl trifluoroacetoacetate (305) resulted in formation of 4-trifluoromethylquinolin-2-one (306) from which 2-brom-4-trifluoromethyl-quinoline (307) was synthesized further. Reaction of compound 307 with pyridines 308 at the presence of a palladium complex as the catalyst resulted in quinoline ligands 309 [185] (Scheme 88). 

Acylketene methodology [10] was also developed for the synthesis of 4-pyrones bearing a polyflnoroalkylthio substituent. The reaction of ethyl trifluoroacetoacetate with fluoroalkanesulfenyl chlorides afforded componnds 12 (Scheme 6). 

Chizhov DL, Sosnovskikh VY, Pryadeina MV, Burgart YV, Saloutin VI, Charushin VN (2008) The first synthesis of 4-unsubstituted 3-(trifluoroacetyl)coumarins by the Knoevenagel condensation of salicylaldehydes with ethyl trifluoroacetoacetate followed by chromene-coumarin recyclization. Synlett 2008 281-285... 

Recently, intermediates 718 were isolated in the reaction of l,l,l-trifluoro-2,4-pentanedione and aminopyrazoles 719 (Scheme 148) [433]. Compounds 718 were formed in CH2CI2 below 10 °C in several minutes. Upon heating to 50 °C or standing at ambient temperature, they underwent dehydration to form the expected aromatic products 720. An analogous intermediate 722 was isolated in the reaction of ethyl trifluoroacetoacetate and aminopyrazole 721 [434]. Intermediates 723 and 724, which correspond to isomerization and partial dehydration of an analogue of 718 - compound 725 - were also detected by NMR [431]. Obviously, formation of these intermediates is responsible for the diminished regioselectivity of the process, which is observed at elevated temperatures or upon change of the solvent. 

Preparation of Fluacrypyrim (301) started with reaction of 0-isopropylisourea hydrochloride and ethyl trifluoroacetoacetate to give pyrimidine 361 (Scheme 80) [292], Alkylation of 361 with bromide 362 (or the corresponding chloride 363 [293,... 

Azeotropic water entrainment. A soln. of ethyl trifluoroacetoacetate in xylene added dropwise during 30 min. to a soln. of o-phenylenediamine in refluxing xylene placed in a flask with a Dean-Stark tube, and heated for an additional hr. 4-trifluoromethyl-lH-l,5-benzodiazepin-2(3H)-one (startg. m. f. 391). Y 88%. F.B.Wigton and M. M. Joullie, Am. Soc. 81, 5212 (1959). 

BINAP-ligated complexes 17-19, which are functionahzed with hydrophilic ammonium units, and successfully apphed them as catalyst for AH in aqueous phase. For instance, complex 17 enables the AH of ethyl acetoacetate in water, providing 100% conversion with 94% ee under relatively mild conditions (40 bar H2 at 50 °C for 16 h), and the catalyst could be recycled at least three times [79a]. In the AH of ethyl trifluoroacetoacetate, a challenging substrate, with Ru-BINAP or its derivatives, the complex 18 dehvered 95% conversion with 70% ee in an acidic aqueous medium (1.0m L water, 0.13 m L acetic acid, and 0.125 m L trifluoroacetic acid) [79c]. 

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