Ethyl 2-chloro-3-oxobutanoates

Cas/liquid reaction 4 [CL 4] Fluorination of ethyl 2-chloro-3-oxobutanoate (ethyl 2-chloroacetoacetate) [15, 16]... 

This microflow processing was also demonstrated using other P-keto esters such as ethyl 2-chloro-3-oxobutanoate [309,273] or ethyl 2-methyl-3-oxobutanoate [273]. Five-and six-ring P-ketoester derivatives such as 3-acetyl-3,4,5-trihydrofuran-2-one (1) [273], 2-acetyl cyclohexanone [273] and ethyl 2-oxocydohexane carboxylate (2) [273] were directly fluorinated as well. 

Quinazoline-4(3// )-thione condenses with ethyl bromocyanoacetate " and ethyl 2-chloro-3-oxobutanoate in the presence of sodium ethoxide in ethanol with sulfur extrusion to form ethyl 2-cyano-2-(quinazolin-4-ylidene)acetate (5, R = CN) and ethyl 2-(quinazolin-4-ylidene)-acetate (5, R = H), respectively. It has been suggested that the initial adduct of quinazoline-4(3//)-thione and a methylene compound is deprotonated to give the corresponding ylide which undergoes electrocyclic closure to a thiirane derivative and then desulfurization. A C - C double bond is formed between the methylene carbon atom and the electrophilic carbon C4, providing an alternative to the Wittig reaction. 

A convenient synthesis of pyridazine-3,4-dicarboxylic acid based on [4 + 2] cycloaddition of an electron deficient diazadiene has been developed (Scheme 102) and carried out on a molar scale. The azadiene is generated in situ from the precursor (124) (prepared from diethyl oxaloacetate and methyl carbazate followed by chlorination with sulfuryl chloride) and trapped with ethyl vinyl ether. The regiospecific cycloaddition gives the tetrahydropyridazine (125) as a mixture of cis and trans isomers which, with bromine in acetic acid, are transformed into diethyl pyridazine-3,4-dicar-boxylate. Saponification gives the diacid in an overall yield of 52% <90JHC579>. In a similar approach from the readily available ethyl 2-chloro-3-oxobutanoate, an efficient route to ethyl 3-methylpyridazine-4-carboxylate has been developed which gives the product in 56% overall yield. This route is claimed to be a practical alternative to the radical ethoxycarbonylation of pyridazines <91JHC1043>. 

Acetyl-5-chloro-3-phenyl Ethyl 2-benzyl-3-oxobutanoate Cone. H Cl 50-90 [7]... 

Two interesting yeast carbonyl reductases, one from Candida magnoliae (CMCR) [33,54] and the other from Sporobolomyces salmonicolor (SSCR) [55], were found to catalyze the reduction of ethyl 4-chloro-3-oxobutanoate to give ethyl (5)-4-chloro-3-hydroxybutanoate, a useful chiral building block. In an effort to search for carbonyl reductases with anti-Prelog enantioselectivity, the activity and enantioselectivity of CMCR and SSCR have been evaluated toward the reduction of various ketones, including a- and /3-ketoesters, and their application potential in the synthesis of pharmaceutically important chiral alcohol intermediates have been explored [56-58]. 

Wada, M., Kataoka, M., Kawabata, H. et al. (1998) Purification and characterization of NADPH-dependent carbonyl reductase, involved in stereoselective reduction of ethyl 4-chloro-3-oxobutanoate, from Candida magnoliae. Bioscience Biotechnology and Biochemistry, 62 (2), 280-285. 

M. Wada, K. Kita, H. Yanase, and S. Shimizu, Stereoselective reduction of of ethyl 4-chloro-3-oxobutanoate by Escherichia coli transformant cells coexpressing the aldehyde reductase and glucose dehydrogenase genes, Appl. Microbiol. Biotechnol. 1999, 53, 486-490. 

CR carbonyl reductase GDH glucose dehydrogenase COBE ethyl 4-chloro-3-oxobutanoate BA butyl acetate. 

Organisms Lactobacillus kefir DSM 20587, Saccharomyces cerevisiae, Candida magnoliae, Bacillus megaterium, Thermoanaerobium brockii, Clostridium beijerinckii, Thermoanaerobacter ethanolicus, Rhodococcus ruber DSM 44541. Solvents ace = acetone iPr = i-PrOH. Substrates WM Wieland-Miescher ketone 4-Me-HP 4-methyl Hajos-Parrish ketone COBE ethyl 4-chloro-3-oxobutanoate. 

Wada M, Kawabata H et al (1999) Occurrence of multiple ethyl 4-chloro-3-oxobutanoate-reducing enzymes in Candida magnoliae. J Biosci Bioeng 87 144-148... 

Glucose-grown cells of G. candidum SC 5469 have also catalyzed the stereoselective reduction of ethyl-, isopropyl-, and tertiary-butyl esters of 4-chloro-3-oxobutanoic acid and methyl and ethyl esters of 4-bromo-3-oxobutanoic acid. A reaction yield of >85% and e.e. of >94% were obtained. NAD+-depen-dent oxido-reductase responsible for the stereoselective reduction of P-keto esters of 4-chloro- and 4-bromo-3-oxobutanoic acid was purified 100-fold. The molecular weight of purified enzyme is 950,000. The purified oxido-reductase was immobilized on Eupergit C and used to catalyze the reduction of (39) to S-( - )-(40). The cofactor NAD+ required for the reduction reaction was regenerated by glucose dehydrogenase. 

Shimizu, S., Kataoka, M., Katoh, M., Morikawa, T., Miyoshi, T., and Yamada, H. 1990a. Stereoselective reduction of ethyl 4-chloro-3-oxobutanoate by a microbial aldehyde reductase in an organic solvent-water diphasic system. Appl. Environ. Microbiol, 56, 2374-2377. 

Cyclopropyl isocyanates react effectively with various nucleophilic reagents. Ammonia and amines yield urea derivatives, " alcohols and phenols afford carbama-tg5,i5 5,164,181,184,185 )V )y-dimethylhydrazine gives a semicarbazide derivative, whereas cyclo-propylammonium chlorides are obtained in refluxing hydrochloric acid. The yields are usually very good. When more highly functionalized nucleophiles are employed, such as the enolate from ethyl 4-chloro-3-oxobutanoate, more complex molecules can be obtained, e.g. the formation of furanone derivative 15. ... 

Another example is the use of heat treatment as a supplement to the screening process. The enantioselectivity of the reduction of ethyl 4-chloro-3-oxobutanoate by Candida magnoliae was improved from 96.6% ee (S) using untreated cells to 99% ee (S) with heat treated cells [67L... 

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