A new synthesis of tafamidis via zinc-MsOH mediated reductive cyclisation strategy

• Published in: Journal of chemical sciences (Bangalore, India) Vol. 133; no. 2
• Main Authors: Karumanchi, Kishore, Natarajan, Senthil Kumar, Gadde, Sunil, Vanchanagiri, Krishna, Moturu, Krishnamurthy V R
• Format: Journal Article
• Language: English
• Published: New Delhi Springer India 01-06-2021; Springer Nature B.V
• Subjects: Aromatic compounds; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Column chromatography; Nitrobenzoic acid; Phenols; Precursors; Rapid Communication; Zinc; synthesis; Tafamidis; zinc-MsOH; reductive Cyclisation; 2-aryl benzoxazoles
• ISSN: 0974-3626; 0973-7103
• DOI: 10.1007/s12039-021-01910-9

A practical zinc-MsOH mediated intra-molecular reductive cyclisation and its application in the synthesis of tafamidis is presented starting from the readily available 3-hydroxy-4-nitrobenzoic acid as a precursor. The key reductive cyclization step involves the use of a combination of the readily available zinc and MsOH as the catalyst system. This methodology provides an attractive route to 2-aryl benzoxazoles from
ortho
-nitro phenols under mild reaction conditions. This methodology is developed on a multi-gram scale and without the need for column chromatography.
Graphic abstract
A new and alternative zinc-MsOH mediated intra-molecular reductive cyclisation and its application in the synthesis of tafamidis is reported starting from the readily available 3-hydroxy-4-nitrobenzoic acid as precursor. This method provides an attractive route to 2-aryl benzoxazoles from
ortho
-nitro phenols under mild reaction conditions.