From a 200 L pilot line, to a 8,000 L production reactor.

An API intermediate whose route needed a strongly irritant material. On the bench it was done by two or three people in respirators taking turns at the addition — about ten minutes each, then out and swap.

At scale, both the addition time and the exposure risk went up. That was the blocking point when the project came to us. We didn't touch the reaction first. We re-laid the area: how the material is decanted, moved and charged, turning an open procedure into a controlled one.

Addition time came down, and the product went from grams to tonnes.

A scale-up project for a p-xylene side-chain chlorination intermediate. Both methyl groups are chlorinated at 120 °C with chlorine gas, one chlorine each. Radical chlorination proceeds stepwise — a little too hot and it overruns, converting one methyl all the way to the di- and tri-chloro by-products. On the bench the tri-chloro fraction stayed low; once the pilot batch was scaled, impurities scaled with it and the product could not meet the client's in-house specification.

The usual approach is to react, discharge, work up, then run a separate distillation column — two separation steps, high energy, high losses. We combined reaction and distillation into a single reactive distillation column, so the product is removed as it forms and over-chlorination is suppressed inside the column.

Temperature and light were fixed as the critical parameters. The dichloro content now releases consistently against the client's specification, batch to batch.

A carbonyl reduction in a tolvaptan intermediate, using KBH4 in methanol. The problem was not yield but impurity: raise the temperature and side reactions follow. The client's in-house limit for this step is 0.1%, and with conventional single-shot charging the pilot batches drifted noticeably — two of them ran close to the line.

We locked the temperature across the whole step to 0–10 °C as a hard process limit, not to be exceeded. KBH4 is charged in portions at set intervals with the charge decreasing batch by batch, the reaction is tracked by HPLC throughout, and work-up was tightened at the same time.

The impurity now sits consistently below 0.05%, roughly half the client's limit.