Acetoacetic acid, ethyl ester, labelled

The magnesium enolates are prepared by treatment of malonic acid half ester either with magnesium ethylate[24],[32] or with isopropylmagnesium bromide[24] or chloride.t26] Ref. [23] describes the synthesis of a 13C-labelled ethyl acetoacetate. Concerning the synthesis of porphyrin / -ketoesters,[3 1 it was noticed that the method via imidazolides is more efficient than the other approach via acid chlorides and sodiomalonic esters. 

Depending on the respective reaction partner, acetic acid esters can react either as C-H acidic compounds or as acylating agents. Both are illustrated by the self-condensation of ethyl [ 1 acetate in the presence of 0.5 equivalent of sodium ethoxide or triphenymethyl sodium to give ethyl [1,3- C2]acetoacetate (Claisen condensation). In the first case, however, because of the relatively low radiochemical yields (40-45%) obtained by this procedure, it is of minor importance for the preparation of labeled ethyl acetoacetate. The deprotonation of alkyl acetates with LiHMDS followed by acylation with unlabeled or labeled acyl halides to labeled give /3-keto esters is discussed in Section 6.4. Claisen condensation of alkyl [ CJacetates with esters lacking a-hydrogens (i.e. ethyl formate, diethyl oxalate, aromatic/heteroaromatic carboxylic acid esters) proceed unidirectionally and are valuable pathways in the synthesis of ethyl [ C]formyl acetate (521. diethyl [ C]-oxaloacetate (53) and ethyl 3-oxo-3-pyrid-3-yl[2- C]acetate (54). The last example... 

There are few carbon- 14-labeled building blocks for which so many preparative procedures are available than for alkyl [ " C]acetoacetates (see Figure 6.82). Most of them start from unlabeled/labeled malonic acid derivatives (mixed dialkyl malonates, monoalkyl malo-nates, Meldrum s acid), which are acylated with labeled/unlabeled acetyl chloride and subsequently converted through selective hydrolysis (or alcoholysis) and decarboxylation. Routes 1 and 2, which have been widely applied, use alkyl fert-butyl malonate or monoalkyl malonate as coupling components, which upon treatment with [l- " C]acetyl chloride and ester cleavage with p-toluenesulfonic acid (Route 1) or by simple acidic workup (Route 2) decarboxylate to give ethyl [3- C]acetoacetate in radiochemical yields of 70-90%. A slightly modified alternative (Route 3) utilizes [l- " C]acetyl imidazolide in... 

Reactions with functionalized alkyl halides significantly enhance the range of application of alkyl [ C]acetoacetates. Alkylation of ethyl [3- C]acetoacetate with halo esters, for example, followed by acid-mediated ketonic cleavage opens access to labeled keto acids/esters, as demonstrated by the synthesis of the [4- C]levulinic acid (307) a y-keto acid. The latter has served as a key intermediate in the synthesis of the 2,3-substituted indole 308 . Step 2 in Figure 6.85, the ketonic cleavage, has recently been shown to be accelerated by a factor of 20 when the reaction is submitted to microwave heating. ... 

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