Also from this week's C&EN, the story of a first scale-up attempt:
The article on continuous processing (C&EN, April 29, page 28) recalls my first experience with the concept. It was in 1988, shortly after I joined DuPont. We had a Grignard reagent to be reacted with an α-chloroketone to make a chlorohydrin intermediate to DuP 860, an antifungal drug candidate. The addition generated so much heat, on scale it couldn’t be kept at the temperature range required for stability over a reasonable reaction period. Instead we fried our first attempt and had to work day and night in the lab running 12 L reactors to make the amount required.
My engineer, Mark Lauritsen, considered our resources at our pilot plant at Chambers Works in New Jersey and asked me for a 4 L jacketed glass reactor. We set up a continuous process in the midst of a bay with two large feed tanks (Grignard reagent and α-chloroketone) leading into the glass reactor and an overflow line leading out to a 100 gal (378.5 L) quench tank. The tiny glass reactor, dwarfed by the other fixed vessels in the bay, seemed so out of place. But once it started up, the continuous process worked perfectly and we made our delivery! Such a logical and simple solution, and my first experience with continuous processing.
Jaan PestiThat's one of the cool things about flow, i.e. the reaction vessel doesn't have to be very big at all to do a big job.
Yardley, Pennsylvania
all is flowing freely until the precipitation clogs the lines
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