3-Fluoroaniline → HCID 86652733, compound

Participants

Reaction Steps

A solution of O-(1-(4-(trifluoromethoxy)phenylsulfonyl)piperidin-4-yl)hydroxylamine (1.02 g, 3.00 mmol) in tetrahydrofuran (20 ml) was added over 1 hour at 0° C. to a solution of trichloromethyl carbonochloridate (890 mg, 4.50 mmol) in tetrahydrofuran (60 ml) and stirred at room temperature for 15 hours. The reaction mixture was concentrated in vacuo and the residue was diluted with tetrahydrofuran (18 ml). 3-Fluoroaniline (100 mg, 0.90 mmol) and N,N-diisopropylethylamine (290 mg, 2.25 mmol) were added and stirred at room temperature for 16 hours. The reaction mixture was quenched with H2O (10 ml) and aqueous 1 N HCl solution (pH=3) and extracted with CH2Cl2 (70 ml×3). The combined organic phase was washed with aqueous NaHCO3 solution and brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography (ethyl acetate/petroleum ether: 33/67) to give 1-(3-fluorophenyl)-3-(1-(4-(trifluoromethoxy)phenylsulfonyl)piperidin-4-yloxy)urea (232 mg, 65%) as a white solid: LCMS: 478 [M+1]+. 1H NMR (DMSO-6) δ: 1.78 (m, 2H), 1.92 (m, 2H), 2.85 (m, 2H), 3.22 (m, 2H), 3.78 (m, 1H), 6.79 (m, 1H), 7.28 (m, 2H), 7.46 (m, 1H), 7.63 (m, 2H), 7.89 (m, 2H), 8.75 (s, 1H), 9.51 (s, 1H).

Provenance & Evidence