Water → (S)-(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 (S)-(2-{[(3,5-bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-methyl}-4-trifluoromethyl-phenyl)-cyclohexyl-methanol (1.81 g, 3.04 mmol) in THF (20 mL) at 0° C. was added sodium hydride (60% dispersion in mineral oil, 254.4 mg, 6.4 mmol). The mixture was stirred at room temperature for 30 minutes, cooled to 0° C. and methyl iodide (1.31 g, 9.2 mmol) was added. The mixture was stirred at room temperature for 5 hours. Water (10 mL) was added and the mixture was extracted with ethyl acetate. Combined organic layers were washed with brine, dried with sodium sulfate and concentrated in vacuo. The residue was purified by chromatography over 25+M Biotage silica column (eluted with 0-30% ethyl acetate in heptane) to afford the title compound as a colorless oil (1.77 g, 96%). 1H NMR (400 MHz, CDCl3) δ ppm 0.93-1.14(m, 5H) 1.18 (d, J=10.79 Hz, 1H) 1.43-1.54(m, 1H) 1.59-1.65(m, J=4.56 Hz, 2H) 1.68-1.74 (m, J=2.49 Hz, 1H) 1.90 (d, J=12.03 Hz, 1H) 3.06 (s, 3H) 4.08 (d, J=7.05 Hz, 1H) 4.21 (s, 3H) 4.71 (d, J=15.77 Hz, 1H) 4.71 (s, 2H) 4.88 (d, J=16.18 Hz, 1H) 7.35 (s, 1H) 7.49 (d, J=8.30 Hz, 1H) 7.55 (d, J=8.30 Hz, 1H) 7.66 (s, 2H) 7.78 (s, 1H). MS (ES+) Calc: 609.2, Found: 610.5 (M+1). [α]D20=36.49 deg (c=10.05 mg/mL, acetone) Determination of absolute configuration of (S)-(3,5-bis-trifluoromethyl-benzyl)-[2-(cyclohexyl-methoxymethyl)-5-trifluoromethyl-benzyl]-(2-methyl-2H-tetrazol-5-yl)-amine

Provenance & Evidence