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

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.