Direct Fluorination of Ethyl 3-Oxobutanoate

Following extensive laboratory studies at the University of Durham, UK, on the direct fluorination of ethyl 3-oxobutanoate in formic acid, scale-out was done from a three- to a nine-channel microstructured reactor, in cooperation with Asahi Class Co. in Yokohama, Japan [77]. 

If the results of the first pilot studies are extrapolated to large-scale synthesis, a two-sided 30-channel device with 60 charmels would be capable of synthesizing about 300 g product per day [77]. By external numbering to 10 reactors, about 3 kg of product per day would result. Such a pilot plant benefits from low expenditure and 

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Figure 5.27 A 30-channel microstructured reactor for the direct fluorination of ethyl 3-oxobutanoate (by courtesy of the Royal Society of Chemistry) [60].

This microflow processing was demonstrated also fluorination of /3-ketoesters such as ethyl 2-chloro-3-oxobutanoate [122,123] or ethyl 2-methyl-3-oxobutanoate [123]. Five- and six-ring /3-ketoester derivatives such as 3-acetyl-3,4,5-trihydrofuran-2-one (1) [123], 2-acetylcyclohexan-one [123], and ethyl 2-oxocydohexane carboxylate (2) [123] were directly fluorinated as well. 

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