Dichloromethane → (+/-)-trans-4-Trifluoromethyl-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexy]phenylacetamide Hydrochloride

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-trifluoromethylphenyl acetic acid (1.45 g, 7.08 mmol) in10 mL of dry CH2Cl2 under a nitrogen atmosphere was added 1-hydroxybenzotriazole hydrate (HOBT) (0.95 g, 7.08 mmol) and stirred. Thereaction mixture was cooled to 0°→5° C. and added solid EDCI ([1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide HCl])(1.35 g, 7.08 mmol) and stirred this temperature for 30 min. A solution (±) 3 (1.0 g, 5.48 mmol) in 10 mL of dry CH2Cl2 was added followed byN,N-diisopropylethylamine (Hunig's Base) (0.915 g, 7.08 mmol). The reactionmixture was stirred for 24 h while warming to the room temperature. The reaction mixture was then poured on to excess of ice-cold saturated aqueous NaHCO3 solution and stirred for 30 min. After dilution with CH2Cl2, the organic was separated, washed with saturated salt solution, and dried over anhydrous Na2SO4. Removal of solvent gave a brown oil which was chromatographed on a silica gel column [solventsystem: CH2Cl2 : CH3OH: 28% NH4OH (99:1:2)] to give the desired product as free base. The hydrochloride salt was prepared from1M etherial HCl and recrystallized from CH2Cl2 :Et2O (1:1)to give (±) 5g HCl as a cream colored solid, 0.68 g (30%); 213°-215° C.; 1H NMR (200 MHz, CDCl3) δ1.02-1.47 (m, 4H), 1.52-2.22 (m, 8H), 2.75-2.90 (m, 2H), 2.94 (s, 3H), 3.07 (m, 1H), 3.37 (m, 1H), 3.62 (d, J=15.0 Hz, 1H), 3.77 (m, 1H), 4.17 (d, J=15.0 Hz, 1H), 4.57 (m, 1H), 7.30 (d, J=8.0 Hz, 2H), 7.38 (d, J=8.0 Hz, 2H). Anal Calcd for C20H27F3N2 O.HCl.0.25H2O: C, 58.68; H, 7.02; N, 6.84. Found: C, 58.68; H, 6.84;N, 6.69.

Provenance & Evidence