Methyl iodide → tert-butyl 4-((2-(((3,5-bis(trifluoromethyl)benzyl)(2-methyl-2H-tetrazol-5-yl)amino)methyl)-4-(trifluoromethyl)phenyl)(methoxy)methyl)piperidine-1-carboxylate

Participants

Reaction Steps

To a solution of tert-butyl 4-((2-(((3,5-bis(trifluoromethyl)benzyl)(2-methyl-2H-tetrazol-5-yl)amino)methyl)-4-(trifluoromethyl)phenyl)(hydroxy)methyl)piperidine-1-carboxylate (62.2 mg, 0.089 mmol) in THF at 0° C. was added sodium hydride (10.7 mg, 0.27 mmol). The mixture was stirred at room temperature for 30 minutes, cooled to 0° C. and methyl iodide (30 μL, 0.5 mmol) was added. The mixture was stirred at room temperature overnight. The reaction was quenched with methanol. Solvent was removed and the residue was purified by chromatography over 12+S Biotage silica column (eluted with 0-30% ethyl acetate in hexanes) to afford the title compound (45.9 mg, 72%). 1H NMR (400 MHz, CDCl3) δ ppm 1.09-1.16 (m, 1H) 1.17-1.29 (m, 2H) 1.43 (s, 9H) 1.58-1.69 (m, 1H) 1.84 (d, J=13.28 Hz, 1H) 2.44-2.58 (m, 2H) 3.04 (s, 3H) 4.04 (d, J=12.45 Hz, 1H) 4.11 (d, J=7.47 Hz, 1H) 4.15 (d, J=7.05 Hz, 1H) 4.20 (s, 3H) 4.68 (d, J=15.77 Hz, 1H) 4.71 (s, 2H) 4.88 (d, J=16.18 Hz, 1H) 7.36 (s, 1H) 7.50 (d, J=8.30 Hz, 1H) 7.57 (d, J=7.88 Hz, 1H) 7.65 (s, 2H) 7.78 (s, 1H). MS (ES+) Calc: 710.3, Found: 711.6 (M+1)

Provenance & Evidence