Methyl iodide → (3,5-Bis-trifluoromethyl-benzyl)-[2-(cyclohexyl-methoxy-methyl)-5-trifluoromethyl-benzyl]-(2-methyl-2H-tetrazol-5-yl)-amine

Participants

Reaction Steps

To a solution of (2-{[(3,5-bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-methyl}-4-trifluoromethyl-phenyl)-cyclohexyl-methanol (35.5 mg, 0.059 mmoles) in THF (0.3 mL) at 0° C. under nitrogen was added sodium hydride (4.8 mg, 0.12 mmoles, 60% dispersion in mineral oil). The reaction was stirred for 30 min., allowing it to warm to room temperature. The reaction mixture was then treated in a dropwise manner with methyl iodide (11 μL, 0.179 mmoles) at 0° C. The ice bath was removed after the addition and the reaction was stirred at room temperature overnight. Solvent was removed in vacuo. The residue was purified using silica gel chromatography over 12+S Biotage silica column (eluted with 0-30% ethyl acetate in hexanes) to yield the title compound (30.1 mg, 83%) as colorless oil. 1H NMR (400 MHz, CDCl3) δ ppm 1.1 (m, 6H) 1.5 (m, 1H) 1.6 (m, 2H) 1.7 (m, 1H) 1.9 (d, J=12.9 Hz, 1H) 3.1 (s, 3H) 4.1 (d, J=7.1 Hz, 1H) 4.2 (s, 3H) 4.7 (d, J=15.8 Hz, 1H) 4.7 (s, 2H) 4.9 (d, J=16.2 Hz, 1H) 7.3 (s, 1H) 7.5 (d, J=7.9 Hz, 1H) 7.6 (d, J=8.3 Hz, 1H) 7.7 (s, 2H) 7.8 (s, 1H). MS (ES+) Calc: 609.2, Found: 610.4 (M+1).

Provenance & Evidence