Photo-oxidation of Cyclopentadiene Using Continuous Processing: Application to the Synthesis of (1R,4S)-4-Hydroxycyclopent-2-en-1-yl Acetate

(1 R,4 S )-4-Hydroxycyclopent-2-en-1-yl acetate is a chiral small building block that was requested to advance several Pfizer programs into the clinic. Pfizer and Syncom partnered to develop a photo-oxidation process of cyclopentadiene using a flow approach followed by subsequent bis-acetylation of the meso diol and final biocatalytic desymmetrization. This continuous process was demonstrated on a 6 g·h –1 input and is amenable to larger scale. The optimization and scale-up of this sequence is described therein.