Ethyl 2-fluoroacetate

Sodium fluoroacetate, which is not volatile and not irritating to the skin, is used as a rodenticide. It is made from CH2ClC02Et and KF, which react to give ethyl fluoroacetate, which is then hydrolysed with NaOH in methyl alcohol. 

Eluoropyridine derivatives can be constmcted from fluoroaUphatic feedstocks. 5-Eluoro-2,6-dihydroxynicotinamide [655-15-OJ, a precursor to the anti-bacterial, enoxacin [74011-58-8] was prepared in 63% yield from ethyl fluoroacetate [459-72-3] ethyl formate [109-94-4], and malonamide [108-13-4] (394). 

Fluoropyrknidine derivatives are of tremendous importance in cancer chemotherapy, eg, 5-fluorouracil [51-21-8] (5-FU). The original 5-fluorouracil process featured a multistep low yield route based on ethyl fluoroacetate (451). Direct fluorination (fluorine) of uracil [66-22-8] gives high yields of 5-FU (452—455). This process has now been commercialized. 

Both methyltriethylphosphonium fluoride and methyltributylphospho-nium fluoride have been prepared The latter generates benzyl fluoride from benzyl chloride in 80% yield and ethyl fluoroacetate from ethyl bromoacetate in 53% yield Methyltnbutylphosphonium fluoride converts 1-bromododecane to a 50 50 mixture of 1-fluorododecane and 1-dodecene Methyltnbutylphosphonium fluoride also quantitatively forms styrene from 1-bromo-1-phenylethane [26] Methyl-tnbutylphosphonium fluonde is the reagent of choice for the conversion of N,N dimethylchloroacetamide to its fluoride, but it is not able to convert chloro-acetonitnle to fluoroacetomtrile Methyltnbutylphosphonium fluoride changes chloromethyl octyl ether to the crude fluoromethyl ether in 66% yield The stereoselectivity of methyltnbutylphosphonium fluoride is illustrated by the reac tions of the 2-tert-butyl-3-chlorooxiranes [27] (Table 2)... 

Alkyl diethylphosphononuoroacetates have been used extensively in ol fi-nanon procedures [69], principally forming the ffJ-a-fluoro-a.P-unsaturated esters with very high stereoselectivity [70] (equation 61) (Table 22). Preparation of the ethyl diethylphosphonofluoroacetate from ethyl fluoroacetate has obviated the necessity to prepare ethyl bromofluoroacetate from bromine fluoride and ethyl diazoacetate [71],... 

Table 7. Products of the Directed Aldol Reaction of Lithium Enolate of Ethyl Fluoroacetate [/S, 19 ...

One of the syntheses of f1 udalanine begins with base promoted condensation of ethyl fluoroacetate and ethyl oxalate to give This is then converted by hydrolytic processes to the insoluble hydrated lithium salt of fluoropyruvate (58). This last is reductively aminated by reduction with sodium boro-deuteride and the resulting racemate is resolved to give D-flu-dalanine (59). 

B. Reactions.—(/) Halides. Whereas ylides are alkylated in the normal way on treatment with a-bromo- or a-iodo-esters, quite different reactions occur with a-fluoro- and a-chloro-acetates. When salt-free ylides were refluxed in benzene with ethyl fluoroacetate or trifluoroacetate normal Wittig olefin synthesis took place with the carbonyls of the ester groups to give vinyl ethers, e.g. (14). On the other hand, methyl chloroacetate with... 

The Arbuzov reaction has been applied for the synthesis of fluorinated carbohydrates. 1,2 3,4-Di-O-isopropylidene-a-D-galactopyran-ose 6-(N,N-diethyl-P-methylphosphonamidite) was treated with ethyl fluoroacetate, to afford 6-deoxy-6-fluoro-l,2 3,4-di-O-isopropylidene-a-D-galactopyranose in 19% yield.241 The corresponding 6-deoxy-6-fluoride was obtained in 60% yield by treatment of l,2 3,4-di-0-isopropylidene-a-D-galactopyranose 6-(dipropylphosphinite) with hexafluoropropene.242 The mechanism of this reaction has been discussed.243,244 In contrast, treatment of 1,2 -.3,4-di-O-isopropylidene-a-D-galactopyranose 6-(tetraethylphosphorodiamidite) with benzoyl fluoride yielded the corresponding 6-benzoate, not the 6-deoxy-6-flu-oride expected.245... 

N-2-Chloroethylfluoroacetamide was also prepared by the direct action of 2 mol. of fluoroacetyl chloride on ethanolamine, although we carried out this reaction with the intention of preparing 2-(fluoroacetamide)ethyl fluoroacetate,... 

It was to be expected that the imino ether hydrochlorides would be hydrolysed in the animal body to give the corresponding fluoroacetate and ammonium chloride, and the toxicities should be roughly the same as those of the fluoroacetates. The results show this to be the case. The compound (VIII iZ = CH2,CH2F) was expectedly more toxic than the other compounds, as this would be hydrolysed to 2-fluoroethyl fluoroacetate which is known to be twice as toxic as methyl or ethyl fluoroacetate,1 as indicated below. 

Ethyl fluoroacetate 2-Chloroethyl fluoroacetate 2-Fluoroethyl acetate 2-Fluoroethyl chloroacetate 2-Fluoroethyl fluoroacetate Phenyl fluorothiolacetate 2-Chloroethyl fluorothiolacetate... 

The synthetic fluorocitric acid, to which reference has been made in the foregoing pages, has been prepared3 in low yield (12 per cent) by the following method from ethyl fluoroacetate 4... 

Higher homologs having a nonterminal fluorine atom were synthesized305 by Claisen condensation of ethyl fluoroacetate with methyl 2,3-O-isopropylidene-DL-glycerate, giving a mixture of the isomeric 2-deoxy-2-fluoro-4,5-0-isopropylidene-DL-3-pentulosonates (540). On... 

Esters of monofluoroacetic acid. e.g. I98 and 2,101 are synthesized from the corresponding chloro or bromo derivatives with potassium fluoride.98 103 The yield for the synthesis of ethyl fluoroacetate (1) ranges from 20 to 75%. Similarly, chloroacetamide and chloroacetonitrile... 

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