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Here, we report a continuous flow protocol for the [3 + 2] cycloaddition of nitrones, in situ generated from oximes, into bicyclic isoxazolidines. This thermal process required very high temperatures to be efficient that were not easily reached in conventional reactors. A couple of examples are presented and in both the flow process showed a greater performance than the batch mode. The process intensification study allowed the generation of 120 g/h of a key pharmaceutical intermediate.

Large-Scale Continuous Flow Transformation of Oximes into Fused-Bicyclic Isoxazolidines: An Example of Process Intensification

see

http://pubs.acs.org/doi/abs/10.1021/op500350y

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