In the synthesis of enantiopure amines, p-methoxyphenyl (PMP) is often the most suitable protecting group, since the protection-deprotection sequence does not change the amine stereochemistry. Most literature procedures describe the deprotection with ceric ammonium nitrate, which involves column chromatography and produces highly toxic waste. Recently, a mild and efficient deprotection using periodic acid was reported1 requiring only acid/base extraction, leading to an overall reduction of costs and a more environmentally benign process.

Deprotection of model substrate

Oxidative cleavage of the PMP group is a fast and exothermic reaction, which limits the feasibility of batch process up-scaling. FutureChemistry has therefore translated this reaction from a batch process to a continuous flow process. FutureChemistry’s typical three-tier approach led to a protocol which can be adapted to any viable PMP protected amine substrate:

       1) Translation of batch process to continuous flow process:
           a) Stock solutions approach, yielding a homogeneous reaction mixture.
           b) Quenching solution to follow the reaction in time.
           c) Flow markers approach to accurately assess reaction parameters.
      2) Automated reaction optimisation.
      3) Out scaling to preparative synthesis

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