Trimethylsilyl iodide → (3R,4S)-N-cyclopropyl-4-(4-(2-(2,6-dichloro-4-methylphenoxy)ethoxy)phenyl)-N-(3-(2-hydroxy-2-methylpropoxy)-5-(3-methoxypropyl)benzyl)piperidine-3-carboxamide

Participants

Reaction Conditions

Reaction Steps

To a solution of tert-butyl (3R,4S)-3-({cyclopropyl[3-(2-hydroxy-2-methyl-propoxy)-5-(3-methoxypropyl)benzyl]amino}carbonyl)-4-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}piperidine-1-carboxylate in acetonitrile (0.02 M) at 0° C. was added iodotrimethylsilane (2 eq.) and stirred for 10 min at 0° C. The reaction was quenched with saturated aqueous NaHCO3 solution and extracted with EtOAc. The combined organic extracts were washed with brine, dried over MgSO4, and concentrated in vacuo. The residue was dissolved in THF (0.2 M) and added tetrabutylammonium fluoride (2 eq.), and the reaction was stirred for 1 h at rt. The reaction mixture was concentrated in vacuo. The crude product was purified by flash column chromatography (SiO2, 7% [2 M NH3 in MeOH] in DCM) to afford the title compound as a colorless oil. 1H NMR (acetone d-6): δ 7.30 (s, 2H), 7.20 (d, 2H), 6.85 (d, 2H), 6.65 (s, 1H), 6.55 (s, 1H), 6.38 (s, 1H), 4.30-4.45 (m, 6H), 3.50-3.80 (m, 4H), 3.00-3.48 (m, 8H), 2.70-2.90 (m, 2H), 2.55 (t, 2H), 2.30-2.40 (m, 4H), 1.70-1.85 (m, 4H), 1.30 (s, 6H), 0.4-0.9 (m, 4H). LRMS [M+H]=713.2

Provenance & Evidence