Development of a catalytic tributyltin hydride cyclisation process

The development of a pilot plant process to prepare the spirocyclic piperid ine (2) from the tetrahydropyridine (4) via a radical cyclisation reaction is described. The pilot plant process involves the use of a catalytic amoun t of tributyltin hydride (0.14 equiv) generated in situ by the reaction of tributyltin chloride with sodium borohydride (1.1 equiv) in 2-propanol/etha nol containing azo-bis(isobutyronitrile) (AIBN). Initial laboratory conditi ons are described as well as the changes made on transfer to the pilot plan t. Measurement of the levels of residual amounts of tin in the batches of ( 2) produced are reported.