Sodium hydride → (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 N-(3,5-bis(trifluoromethyl)benzyl)-2-methyl-2H-tetrazol-5-amine (26.7 mg, 0.082 mmol) in DMF (1 ml) at 0° C. under nitrogen was added sodium hydride (6 mg, 0.1 mmol, 60% dispersion in mineral oil). The reaction was stirred for 30 minutes while allowing it to warm to room temperature. The reaction mixture was then treated with (S)-2-bromomethyl-1-(cyclohexyl-methoxy-methyl)-4-trifluoromethyl-benzene (25 mg, 0.068 mmol) at 0° C. The ice bath was removed after the addition and the reaction was stirred at room temperature overnight. Water was added and the mixture was extracted with ethyl acetate. Combined organic layers were washed with water, brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by chromatography on 12+S Biotage silica column, eluting with ethyl acetate in heptane 0-30% (10CV) and 30% (3CV) to yield the title compound (20 mg, 48%) as colorless oil. 1H NMR (400 MHz, CDCl3) δ ppm 1.07 (m, 4H) 1.2 (m, 2H) 1.46 (m, 1H) 1.57 (m, 2H) 1.61(m, 1H) 1.90 (d, J=12.4, 1H) 3.06 (s, 3H) 4.08 (d, J=7.1, 1H) 4.2 (s, 3H) 4.70 (d, J=15.7, 1H) 4.89 (d, J=15.7, 1H) 7.35 (s, 1H) 7.50 (d, J=7.9, 1H) 7.55 (d, J=7.9, 1H) 7.65 (s, 2H) 7.77 (s, 1H). [α]D20=−26.6 deg (c=13 mg/mL, acetone).

Provenance & Evidence