RSS-Feed abonnieren
DOI: 10.1055/s-0040-1706388
Synthesis of Ritobegron Ethyl Hydrochloride
Development of an Efficient Scale-up Synthesis Method for β3-Adrenergic Receptor Agonist, Ritobegron Ethyl Hydrochloride.
Org. Process Res. Dev. 2020;
24: 1675-1682
DOI: 10.1021/acs.oprd.0c00278
Key words
ritobegron - β3 receptor agonist - hydroxyalkylation - reductive deoxygenation - trimethylsilyl iodide
Significance
Ritobegron ethyl hydrochloride is a prodrug of ritobegron, a β3-adrenergic receptor agonist that was a lead for the treatment of overactive bladder. In the second-generation synthesis depicted, hemiacetal G enabled convenient removal of impurities by crystallization. This six-step synthesis delivered 69 kilograms of API in 43% overall yield compared with 27% overall yield for the five-step, first-generation synthesis.
#
Comment
Salient features include (1) the base-promoted hydroxyalkylation of xylenol A with glyoxal dimethylacetal (B) to give C in 80% yield with high regioselectivity (para/ortho = 97:3) and (2) the reductive deoxygenation of benzylic alcohol E without detriment to the dimethylacetal using trimethylsilyl iodide generated in situ.
#
#
Publikationsverlauf
Artikel online veröffentlicht:
17. November 2020
© 2020. Thieme. All rights reserved
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany