Ethyl 4,4,4-trifluoroacetate

The ketone shown was prepared in a three step sequence from ethyl trifluoroacetate The first step in the sequence involved treating ethyl tnfluoroacetate with ammonia to give a compound A Compound A was in turn converted to the desired ketone by way of a compound B Fill in the missing reagents in the sequence shown and give the structures of compounds A and B... 

CijH,7NO, 87848-98-4) see Acrivastine ethyl 3-[4-(o-tolyl)-l-piperazinyl]propionate (CifiH24N202 63853-99-6) see Dapiprazole ethyl A-(p-tolylsulfonyl)carbainate see under ethyl 4-toluenesulfonylcarbamate ethyl trifluoroacetate... 

Diethyl succinate had been introduced into a mixture of sodium hydride and ethyl trifluoroacetate at 60°C. The medium detonated ten to twenty minutes after starting the addition of succinate. Two accidents that are identical to this one have been described. 

Ethyl trifluoroacetate, Sodium hydride See Sodium hydride Diethyl succinate, etc. 

Acylation of diethyl succinate by ethyl trifluoroacetate in presence of sodium hydride and in absence of a solvent is hazardous, fire or explosion occurring on 2 occasions some 10-20 min after adding a tittle of the succinate to the hydride-trifluoroacetate premixture at 60°C. Presence of a solvent appears to eliminate the hazard. 

Attempted reduction of vinyl acetate yields a mixture containing 8% ethyl acetate and 3% ethyl trifluoroacetate after 10 hours. The amounts of the two esters change to 13% and 12%, respectively, at reaction times beyond 60 hours.234 Vinyl trifluoroacetate does not undergo reduction under these conditions, even after 75 hours.234... 

Many of these reactions are not observed at all when the relevant groups are allowed to come together in bimolecular processes in aqueous solution. For mechanistic work involving intermolecular reactions, therefore, it is necessary to use activated substrates. Much of what we know about the relevant reactions of esters, for example, comes from studies using aryl esters like p-nitrophenyl acetate, or acyl-activated compounds like ethyl trifluoroacetate (Bruice and Benkovic, 1966 Jencks, 1969 Bender, 1971). 

The procedure described here illustrates a general and inexpensive two-step method for the stereoselective preparation of new, variously substituted I-CF3 epoxy ethers from ethyl trifluoroacetate.2-3.4 The first step of this procedure is a Wittig olefination of ethyl trifluoroacetate in which sodium hydride is used for the generation... 

Ethyl trifluoroacetate Acetic acid, trifluoro-, ethyl ester (8,9) (383-63-1) m-Chloroperoxybenzoic acid Peroxybenzoic acid, m-chloro- (8) Benzocarboperoxoic acid, 3-chloro- (9) (937-14-4)... 

Ethyl trifluoroacetate (2), obtained from Aldrich Chemical Company, Inc., is distilled and stored over sodium bicarbonate before use. 

Kutsuna, S., Chen, L., Abe, T., Mizukado, J., Uchimaru, T., Tokuhashi, K., and Sekiya, A. Henry s law constants of 2,2,2-tri-fluoromethyl formate, ethyl trifluoroacetate, and non-fluorinated analogous esters, Atmos. Environ., 39(32) 5884-5892,2005. 

The establishment of the stereocenter in efavirenz provides a challenging goal for the synthetic chemist (Pierce et al., 1998 Thompson et al., 1995). The synthesis starts by treating 4-chloroaniline with pivaloyl chloride under biphasic conditions to provide the desired amide 10 (Scheme 6.2). Ortho metallation as directed by the amide is accomplished with two equivalents of n-butyllithium (or w-hexyllithium) in tetramethylethylene diamine (TMEDA) and MTBE. The resulting dianion is quenched with ethyl trifluoroacetate to provide pivaloylamide ketone 11 (Euhrer and Gschwend, 1979). The amide is hydrolyzed in situ to provide the trifluoroketone hydrate hydrochloride 12, which crystallizes from the reaction mixture (>98% pure). 

Figure 2.43 Acylation reactions with ethyl trifluoroacetate.

Figure 18. Enantiomer separation of Q 2-1-mcthyl-2-(l-methylethenyl)cyclobutyl]ethyl trifluoroacetate (grandisol) and 2-chloroalkanes on heptakis(2,3,6-tri-0-pcntyl)- -cyclodextrin (42 m glass capillary column, 50 1 bar hydrogen)174.

The dipolarophile was prepared in a short (three-step) sequence from methyl phenyl sulfone (38% overall yield) and ethyl trifluoroacetate. Desulfonation, followed by reductive N-0 cleavage afforded the syn aminoalcohols [246]. Conjugate additions to the sulfone were described some years earlier [247] more recently, trifluoromethyl pyrroles have been synthesised from the nitro-propene [248]. 

With regard to the synthesis of celecoxib (1), several routes were described in the 1995 patent by G. D. Searle As shown in Scheme 1, dione 7 was prepared by the Claisen condensation of 4-methylacetophenone with ethyl trifluoroacetate in the presence of NaOMe in methanol under reflux. Subsequent diarylpyrazole formation from the condensation of dione 7 and 4-sulfonamidophenylhydrazine hydrochloride then delivered... 

The key intermediate chloromethyloxadiazole 18 was prepared in two steps from inexpensive, commercially available materials as shown in Scheme 5.10. Bishydrazide 19 was prepared in a one-pot procedure by reaction of 35% aqueous hydrazine with ethyl trifluoroacetate in acetonitrile and subsequent addition of chloroacetyl chloride and base. This procedure affords the unsymmetrical bis(hydrazide) 19 in higher than 95% assay yield. While a number of dehydrating agents were found to be effective in the dehydration to prepare 18, phosphorus oxychloride was chosen because of its low cost and relatively benign waste stream. Sub-stoichiometric (0.3 equiv.) amounts were found to be as effective as full equivalents in the reachon when used in conjunction with catalyhc amounts of DMAP as a nucleophilic catalyst. The entire sequence was transformed into a one-pot through process in order to improve efficiency. Following the cyclization, an aqueous work-up was performed and the organic extracts carried directly into the next step. 

Many continuous processes are used to prepare early pharmaceutical intermediates, but Pfizer recently presented a continuous process to prepare the API itself. A continuous process to prepare the anti-inflammatory drug celecoxib was described (Scheme 11.3) [6]. The batch process for celecoxib consists of two steps (1) a base-mediated Claisen reaction between 4-methylacetophenone and ethyl trifluoroacetate, and (2) an acid-mediated pyrazole condensation between enolate intermediate 8 and hydrazine 9 giving celecoxib (Scheme 11.4) [7]. Continuously flowing the Claisen reaction step 1 into the pyrazole condensation step 2 offers the advantages of directly telescoping continuous processing steps, as described in the introduction to this chapter. 

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