A-Chloroacetoacetic acid, ethyl ester

Chlormolysis of tetraethylthiuram disulfide, 35, 55 Chloroacetamide, 30, 22 Chloroacetic acid, 39, 78 a-Chloroacetoacetic acid, ethyl ester, 33, 43, 45... 

Meguro and co-workers used this method, among others, to prepare a variety of potential antidiabetic agents. For example, cyclization of cyclohexanecarbox-amide with ethyl 4-chloroacetoacetate gave 2-cyclohexyl-4-oxazoleacetic acid 199, albeit in poor yield (Scheme 1.54). Similarly, Ohkubo and co-workersprepared 4-(nitrophenyl)-2-phenyl-5-oxazolecarboxylic acid ethyl esters 200a and 200b as precursors to potential cerebral protective agents. 

A first group of ISPR systems, most commonly with reductions, is those using the addition of a resin or porous adsorbent to remove the product. Early work on ketone reduction showed already that hydrolysis and also loss of ee could be overcome by maintaining low concentrations of the substrate in the reaction. One successful approach involves the controlled release of the substrate from a resin placed in the reaction media. For example, Amberlite XAD-2 resin enhanced the asymmetric reduction of ethyl 4-chloroacetoacetate to (S)-4hydroxybutyric acid ethyl ester catalyzed by yeast [34]. In the subsequent development of the technolt, the approach was extended to simultaneous substrate supply and product removal. A similar approach was developed for the asymmetric reduction of 6-bromo-P-tetralone [35]. 

The ammonium formate in formic acid procedure has rendered possible the first preparation of isomeric 4,5-disubstituted oxazoles.03101 Bredereck, Gompper, and Reich101 have reported the anomalous behavior of certain long-chain a-bromo ketones a single a-bromo ketone on reaction with ammonium formate in formic acid gives a mixture of two isomeric oxazoles. Refluxing of a-bromo ketones or of a-chloro-/3-keto esters with ammonium acetate in acetic acid results in the formation of substituted 2-methyl-oxazoles.40 102 Ethyl a-chloroacetoacetate on heating with ammonium carbonate or formamide in formic acid yields 4-methyloxazole-5-carboxylic ester.40 103... 

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