4-Iodo-2-(trifluoromethyl)pyridine

4-Iodo-2-(trifluoromethyl)pyridine is used as a reagent in the synthesis of aminoisoindoles as β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors which exhibit in vivo brain reduction of β-amyloid peptides.

4-Iodo-2-(trifluoromethyl)pyridine could be cleanly deprotonated by LIDA in tetrahydrofuran at –75 °C[1]. Trapping of the organometallic intermediates with dry ice followed by neutralization gave the 4-iodo-2-(trifluoromethyl)pyridine-3-carboxylic acid (16, 31%). a: LIDA in THF at –75 °C for 2 h; b: (1.) Excess solid carbon dioxide, (2.) Hydrochloric acid.

[1] Schlosser M, et al. Further Metalations and Functionalizations of Chloro-, Bromo- and Iodo(trifluoromethyl)pyridines. Synthesis, 2004; 10: 1619-1624.