01755nas a2200205   4500008004100000022001400041245009300055210006900148260000800217300001200225490000700237520104000244653003401284653001901318653002201337653002701359100002201386700002301408856011801431       2025                        eng d  a1083-616000aContinuous flow telescopic synthesis of 3-methoxy propiophenone by the grignard reaction0 aContinuous flow telescopic synthesis of 3methoxy propiophenone b  cJAN  a450-4590 v293 a<p>
	The synthesis of 3-methoxypropiophenone 1, a crucial intermediate in the production of the analgesic tapentadol hydrochloride, was investigated using a multistep continuous flow process. The approach is based on the Grignard reaction. A series of continuously stirred tank reactors (CSTRs) were employed: the first reactors facilitated the continuous generation of Grignard reagents 3, which then reacted with propionitrile in the next CSTR to yield 1. This was followed by quenching, neutralization, and phase separation, conducted under varying temperatures and residence times. When compared to a 50% yield from an optimized batch synthesis protocol, a continuous flow synthesis helped achieve an 84% yield of the desired product in a much shorter reaction time. A kinetic model was developed to predict the Grignard reagent formation and product yield, revealing that the mass transfer effect is insignificant at a higher stirring rate. The approach is highly scalable for the synthesis of pharmaceutical intermediates.</p>
10abatch and continuous reaction10aflow chemistry10aGrignard reaction10aheterogeneous kinetics1 aWankhede, Pranali1 aKulkarni, Amol, A.  uhttps://library.ncl.res.in/content/continuous-flow-telescopic-synthesis-3-methoxy-propiophenone-grignard-reaction