The 2,2,2-trifluoroethoxy group was identified as an alternative leaving group in nucleophilic aromatic substitution (S<sub>N</sub>Ar) reaction where the corresponding heterocyclic chloride was found to be hydrolytically unstable. This group imparts shelf stability to the template while maintaining reactivity toward nucleophiles, which is an important consideration during the development of scalable processes. The 2,2,2-trifluoroethoxy ethers were also tolerant aqueous Suzuki conditions, permitting sequential Suzuki/S<sub>N</sub>Ar processes inaccessible to the heterocyclic chlorides.

2,2,2-Trifluoroethoxide: Alternative leaving group for hydrolytically unstable heterocyclic chlorides

256th National Meeting (2018)

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