Development of Safe, Scalable Nitric Acid Oxidation Using a Catalytic Amount of NaNO₂ for 3-Bromo-2,2-bis(bromomethyl)propanoic Acid: An Intermediate of S-013420

A safe, scalable process was developed for nitric acid oxidation of 3-bromo-2,2-bis(bromomethyl)propan-1-ol ( 2 ) to give 3-bromo-2,2-bis(bromomethyl)propanoic acid ( 3 ), an intermediate in the synthesis of S-013420 ( 1 ). The key points are the use of a catalytic amount of NaNO 2 and addition of the starting material in portions. We achieved 3,000 L scale pilot production.