Development of a continuous process for the industrial generation of diazomethane

The development of a safe process for the industrial generation of diazomethane is described. Diazomethane is produced and consumed in a continuous process capable of generating between 50 and 60 tonnes per year whilst the maximum inventory is maintained at less than 80 g. The diazomethane production unit is part of an integrated multistage continuous process that produces key intermediates for the latest generation of HIV protease inhibitor drugs. The use of diazomethane in this role has facilitated a direct cost-effective route to compounds such as (2S,3R)-3-(N-benzyloxycarbonyl)-amino-1-chloro-4-phenylthiobutan-2-ol that can be produced in 82% yield from N-benzyloxycarbonyl-S-phenyl-L-cysteine.