Ultrafast synthesis of 2-(benzhydrylthio)benzo[]oxazole, an antimalarial drug, an unstable lithium thiolate intermediate in a capillary microreactor

• Published in: Reaction chemistry & engineering 2020-05, Vol.5 (5), p.849-852
• Main Authors: Ramanjaneyulu, Bandaru T, Vidyacharan, Shinde, Ahn, Gwang-Noh, Kim, Dong-Pyo
• Format: Article
• Language: English
• ISSN: 2058-9883
• DOI: 10.1039/d0re00038h

We present an ultrafast approach for the synthesis of 2-(benzhydrylthio)benzo[ d ]oxazole, an antimalarial drug, in 75% yield from benzo[ d ]oxazole-2-thiol and benzhydryl bromide via an unstable lithium thiolate intermediate in the presence of n -BuLi. The precisely controlled two-step reaction at room temperature in a simple capillary microreactor enables a drastic decrease of the synthesis time to milliseconds (580 ms) from 10 min in a flask. Furthermore, a simple continuous-flow operation of the low cost reactor readily realizes a high throughput, leading to a several gram scale production (approximately 4 g per 13.3 min) at a very high flow rate of 7.6 ml min −1 . We present an ultrafast approach for the synthesis of 2-(benzhydrylthio)benzo[ d ]oxazole, an antimalarial drug, in 75% yield from benzo[ d ]oxazole-2-thiol and benzhydryl bromide via an unstable lithium thiolate intermediate in the presence of n -BuLi.