Continuous Hydrolysis and Liquid–Liquid Phase Separation of an Active Pharmaceutical Ingredient Intermediate Using a Miniscale Hydrophobic Membrane Separator
Continuous Hydrolysis and Liquid–Liquid Phase Separation of an Active Pharmaceutical Ingredient Intermediate Using a Miniscale Hydrophobic Membrane Separator
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DOI：
10.1021/op200242s
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发表时间：
2012-03
影响因子：
3.4
通讯作者：
A. E. Cervera-Padrell;S. T. Morthensen;D. Lewandowski;Tommy Skovby;S. Kiil;K. Gernaey
中科院分区：
文献类型：
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作者：
A. E. Cervera-Padrell;S. T. Morthensen;D. Lewandowski;Tommy Skovby;S. Kiil;K. Gernaey
活性药物成分中间体的连续水解和随后所得有机相和水相的液-液（L-L）分离已经使用连接到微型疏水膜分离器的简单PTFE管式反应器实现。在THF中通过格氏反应以连续模式获得的醇盐产物与酸性水反应以产生含有镁盐的部分可混溶的有机相和水相。尽管部分THF-水可溶解性，但使用具有28 cm 2活性面积的PTFE膜，在不同流量比下，在高达40 mL/min的总流速下，可以分离两相。在高达80 mL/min的总流速下实现了水和甲苯的较低挑战性分离，并有可能实现甚至更高的流速。从实验和物理的角度比较了膜分离器和板式聚结器的可操作性和灵活性。对表面张力驱动的液-液分离进行了一般性分析，
Continuous hydrolysis of an active pharmaceutical ingredient intermediate, and subsequent liquid–liquid (L-L) separation of the resulting organic and aqueous phases, have been achieved using a simple PTFE tube reactor connected to a miniscale hydrophobic membrane separator. An alkoxide product, obtained in continuous mode by a Grignard reaction in THF, reacted with acidic water to produce partially miscible organic and aqueous phases containing Mg salts. Despite the partial THF–water miscibility, the two phases could be separated at total flow rates up to 40 mL/min at different flow ratios, using a PTFE membrane with 28 cm2 of active area. A less challenging separation of water and toluene was achieved at total flow rates as high as 80 mL/min, with potential to achieve even higher flow rates. The operability and flexibility of the membrane separator and a plate coalescer were compared experimentally as well as from a physical viewpoint. Surface tension-driven L-L separation was analyzed in general terms, ...