matched the yields reported, product concentrations were lower,
which indicated precipitation of the product. Reported yields
were obtained by flushing the reactor system with hydrogen
chloride in DME at the end of a run and thus contain some
degree of start-up and shutdown material. Steady state operation
of the microreactor system was possible for up to two hours
before flushing the reactor with HCl became necessary. Precipi-
tation of the carboxylate occurred as a uniform wall coating,
which suggests that ultrasonic forces developed for handling solid
aggregates might be ineffective.39,40 Application of automated
reactor switching and cleaning protocols using two parallel
reactors has been discussed for microfluidic applications and
would enable the processes reported here to be operated without
down time.41,42 The high cost of the solvents used in this study
can be offset by implementation of recycling and purification
schemes at production scales. However, these approaches are
seldom practical in a lab-scale study.
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K.N. thanks the Novartis-MIT Center for Continuous
Manufacturing for financial support.
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This journal is The Royal Society of Chemistry 2012