The invention belongs to the technical field of
organic synthesis, and relates to a preparation method of
cimetidine, in particular to a process for synthesizing
cimetidine through
continuous flow reaction. According to the process,
cyanamide and
methyl isocyanate are taken as initial raw materials and are accurately pumped into a microchannel
continuous flow reactor according to a certain
molar ratio, and the N-cyano-N '-methylurea intermediate is efficiently and controllably synthesized at a specific temperature. And then, synchronously pumping a 2-(((5-methyl-1H-
imidazole-4-yl) methyl) sulfo) ethyl-1-amine
hydrochloride solution and the N-cyano-N '-methylurea intermediate into a subsequent
continuous flow reaction module, introducing the reaction liquid into an online
drying device with a
molecular sieve in real time, and promoting efficient
nucleophilic addition reaction through continuous water removal, thereby obtaining the N-cyano-N'-methylurea intermediate. Finally, the
cimetidine is obtained at a high yield. The method has the outstanding advantages of mild conditions, high yield, stable product quality, easiness in large-scale amplification and the like, and is a new generation of cimetidine preparation technology which is green, safe and efficient and has important industrial application value.