Methane → 3-(4-Fluorophenyl)-1-methyl-1-(1-(3-(trifluoromethyl)phenylsulfonyl)piperidin-4-yloxy)urea

Participants

Reaction Steps

A solution of N-methyl-O-(1-(3-(trifluoromethyl)phenylsulfonyl)piperidin-4-yl)hydroxylamine (130 mg, 0.384 mmol) in tetrahydrofuran (10 ml) was added to a suspension of trichloromethyl chloroformate (91.3 mg, 0.46 mmol) and activated charcoal (20 mg) in tetrahydrofuran (35 ml) at 0° C. over 30 minutes. After stirring at room temperature for 18 hours, the reaction mixture was filtered over silicagel and the filtrate was concentrated in vacuo. The residue was dissolved in tetrahydrofuran (15 ml), 4-fluoroaniline (65 mg, 1.13 mmol) and N,N-diisopropylethylamine (148 mg, 1.15 mmol) were added and the whole was stirred at room temperature for 18 hours. The reaction mixture was concentrated in vacuo and the residue was diluted with ethyl acetate (50 ml), washed with H2O (20 ml×2), brine (20 ml×2), dried over Na2SO4 and concentrated in vacuo. The residual solid was recrystallized from diethyl ether to give 3-(4-fluorophenyl)-1-methyl-1-(1-(3-(trifluoromethyl)phenylsulfonyl)piperidin-4-yloxy)urea (89.5 mg, 49%) as a white solid. LCMS: 476 [M+1]+. 1H NMR (DMSO-d6) δ: 1.79 (m, 2H), 1.98 (m, 2H), 2.59 (m, 2H), 3.0 (s, 3H), 3.62 (d, 2H), 3.89 (m, 1H), 7.11 (t, 2H), 7.50 (m, 2H), 7.94 (q, 2H), 8.12 (q, 2H), 8.70 (s, 1H).

Provenance & Evidence