Main > MICROCHEMISTRY > Applications > AnAlgesics>Tramadol > Co.: USA. J (Synthesis Description) > Description
Author and her coworkers have studied the metal-halogen exchange step in the reaction of 3-bromoanisole with n-butyllithium to obtain 3-methoxyphenyllithium. The aryllithium compound is stable only at cryogenic temperatures and can be reacted in batch mode with (±)-2-[(dimethylamino)methyl]cyclohexanone to give, with high stereoselectivity, an alternative synthesis of the analgesic tramadol.
Because they have just one microreactor system, Co. s scientists made the aryllithium intermediate at -14 șC using a 17-second reactor residence time and then reacted it in batch mode with cyclohexanone (as a model compound) to achieve an 87% yield and 54-g-per-hour throughput. With two successive microreactors, Author says, they could have fed the unstable intermediate directly into the second reactor to complete the synthesis sequence in a favorable continuous mode.
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