Integrating Process Development and Safety Analysis for Scale-Up of a Diborane-Generating Reduction Reaction

• Published in: Organic process research & development Vol. 27; no. 4; pp. 763 - 774
• Main Authors: Armstrong, Brittany M., Behre, Taylor, Turnbull, Ben W. H., Bishara, Daniel, Hartmanshenn, Clara, McCarthy, Erin, Whittington, Michael, Ji, Yining, Jenks, Anna, Desmond, Richard, Muzzio, Daniel J., Corry, James, Zhao, Ralph, Kuhl, Nadine, Chung, Cheol K.
• Format: Journal Article
• Language: English
• Published: American Chemical Society 21.04.2023
• Subjects: process safety; calorimetry; gas generation; hazardous reaction; process development; diborane; scale-up; exothermic reaction; infrared spectroscopy

Our company has developed a robust and scalable process to synthesize an amino alcohol tosylate salt, a penultimate intermediate in the synthesis of nemtabrutinib. A key reaction in this synthetic sequence is a reductive acetal ring opening using boron trifluoride diethyl etherate as a Lewis acid an...