Structural Development Studies of Subtype-Selective Ligands for Peroxisome Proliferator-Activated Receptors (PPARs) Based on the 3,4-Disubstituted Phenylpropanoic Acid Scaffold as a Versatile Template

Scheme 3

The synthetic route to TIPP-204. Reagents and conditions: (m) nBuI, K₂CO₃, DMF, rt., (n) NaBH₄, EtOH, rt., (o) PBr₃, ether, 0^°C, (p) (1) (R)-4-benzyl-3-butyryloxazolidin-2-one, LiHMDS, THF, −40^°C–−10^°C, (2) benzyl 5-bromomethyl-2-butoxybenzoate, THF, −40^°C–−10^°C, (q) H₂, 10% Pd–c, AcOEt, rt., (r) BH₃-tetrahydrofuran, THF, 0^°C, (s) activated MnO₂, CH₂Cl₂, rt., (t) 2-fluoro-4-trifluoromethylbenzamide, triethylsilane, trifluoroacetic acid, toluene, reflux, (u) LiOH H₂O, H₂O₂, THF-H₂O, 0^°C.