Organic process research and development p. 286 - 293 (2020)
Update date:2022-08-11
Topics:
Bangal, Mukund N.
Deshmukh, Dattatray G.
Kalawade, Kaustubh A.
Mathad, Vijayavitthal T.
After successful development of a manufacturing process for the Mirabegron (1) at the laboratory scale, a muddled situation was aroused during the scale-up batches, wherein sodium borohydride-iodine (NaBH4-I2) mediated reduction of nitro-amide 4 ended up with substantial amounts (~10%) of unspecified impurity in the nitro-amine intermediate 5. On the basis of the structure elucidation and meticulous investigation, a reaction path for its genesis during the process was identified and an efficient mechanism proposed to arrest its formation. In-situ generated nickel boride (Ni2B) due to reaction of NiI2 (corrosion product) with NaBH4 followed by electrophilic attack of THF (solvent) was found to be the reason for the formation of impurity (8a). Execution of subsequent batches with proper controls arrested this impurity and successfully provided the Mirabegron with the desired quality.
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(2021)