Hydrochloric Acid → 4-(2-(((3,5-Bis(trifluoromethyl)benzyl)(2-methyl-2H-tetrazol-5-yl)amino)methyl)-4-(trifluoromethyl)phenyl)-4-methoxycyclohexanecarbonitrile

Participants

Reaction Steps

To a solution of N-(3,5-bis(trifluoromethyl)benzyl)-2-methyl-2H-tetrazole-5-amine (285 mg, 0.877 mmol) in anhydrous THF (5 mL) was added sodium hydride (60% dispersion in mineral oil, 105 mg, 2.63 mol) and the mixture was stirred for 5 minutes then a solution of 4-(2 (bromomethyl)-4-(trifluoromethyl)phenyl)-4-methoxycyclohexanecarbonitrile (330 mg, 0.877 mmol) in anhydrous THF (5 mL) was added. A further aliquot of sodium hydride (52 mg, 1.3 mmol) was added. The solution was stirred at room temperature for 72 hours. Water and 2 N HCl (5 mL) were added and the mixture was extracted with ethyl acetate (3×20 mL). The combined organics were dried with anhydrous sodium sulfate and concentrated under reduced pressure to give a yellow oil (0.65 gm). This material was initially purified by flash chromatography on a 40 g RediSep column (Teledyne Isco Inc., Lincoln Nebr.) (eluted with 5-75% ethyl acetate in heptane) and finally purified on 1 mm silica gel rotor (Chromatotron, Harrison Research) (eluted with 20-70% dichloromethane in heptane) to yield the title compound as a colorless foam (134 mg, 24.6%). 1H NMR (400 MHz, CDCl3) δ 7.74 (s, H) 7.67(s, 2H) 7.44 (d, J=5.81 Hz, 2H) 7.29 (d, J=8.72 Hz, 1H) 5.01 (s, 2H) 4.76 (s, 2H) 4.15 (s, 3H) 2.87(s, 3H) 2.43(m, 1H) 2.20(d, J=12.45 Hz, 2H) 1.99(m, 2H) 1.55(m, 4H). LC-MS calc. 620, found 621.5 (M+H)

Provenance & Evidence