An updated synthesis of octa-acid

Octa-acid 1 is a water-soluble deep-cavity cavitand devised in our labs that has found utility in a number of research groups. The host has been used to investigate hydrophobic solvation and Hofmeister effects, control photophysical and physicochemical properties, modulate the reactivity of encapsulated guests, and as a tool to engender novel separation protocols. The synthesis of 1 has largely centered around its formation from cavitand 2, a host that is itself most readily synthesized on the multi-gram-scale but in a crude form (>75% purity). In this Methods Article we reveal improvements in the synthesis of 2, as well as a new synthetic strategy that efficiently converts crude 2 into pure 1. This new synthesis provides access to 1 in only a five-step linear sequence, shortening the total reaction time from previous methods, improving the purity, and increasing the final yield of pure 1. We therefore anticipate that the described protocols will be of interest to any research group seeking to utilize octa-acid in their studies.