NaBH4/MeOHを用いたケトンの還元反応におけるin situ反応解析
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概要
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In development of a manufacturing process for drug candidate, to ensure the safety of manufacturing is required for process chemists. It’s one of the useful procedures to understand the reaction behavior for the purpose of the safety consideration. In a process development for a ketone reduction with NaBH4/MeOH, we measured the reaction behavior of using a reaction calorimetry (RC1eTM), gas measurement devise and in situ particle counter (FBRM®). It was found that the combination of these reagents has the induction period and latent, abrupt release of heat and gas evolution. Furthermore, the measurement of the particle counts revealed that the induction period was caused by the insolubility of NaBH4 in THF and the disproportionation of NaBHx(OMe)4-x to NaBH4.
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