4-Chlorobenzoic Acid → 4-chloro-N-(1-(3-(trifluoromethyl)phenylsulfonyl)piperidin-4-yloxy)benzamide

1-(3-Dimethylaminopropyl)-3-ethylcarboiimide hydrochloride (138 mg, 0.72 mmol) was added to a solution of O-(1-(3-(trifluoromethyl)phenylsulfonyl)piperidin-4-yl)hydroxylamine (195 mg, 0.60 mmol), 1-hydroxybenzotriazole (97.0 mg, 0.72 mmol), 4-chlorobenzoic acid (94.0 mg, 0.60 mmol) and N,N-diisopropylethylamine (233 mg, 1.80 mmol) in N,N-dimethylformamide (6 ml). The reaction mixture was stirred at room temperature for 17 hours and quenched with H2O (8 ml) and aqueous 1 N HCl solution (pH=3). The aqueous phase was extracted with CH2Cl2 (20 ml×3) and 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/hexane: 67/33) to give 4-chloro-N-(1-(3-(trifluoromethyl)phenylsulfonyl)piperidin-4-yloxy)benzamide (172 mg, 62%) as a white solid: LCMS: 463 [M+1]+. 1H NMR (DMSO-d6) δ: 1.70 (m, 2H), 1.90 (m, 2H), 3.01 (m, 2H), 3.13 (m, 2H), 3.98 (d, 1H), 7.51 (d, 2H), 7.68 (m, 2H), 7.95 (m, 2H), 8.11 (m, 2H), 11.6 (s, 1H).

1. customquenched with H2O (8 ml) and aqueous 1 N HCl solution (pH=3)
2. extractionThe aqueous phase was extracted with CH2Cl2 (20 ml×3)
3. washthe combined organic phase was washed with aqueous NaHCO3 solution and brine
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe residue was purified by column chromatography (ethyl acetate/hexane: 67/33)

ORD record

ord-f7467d9122fc4c34b876572f0ec5bfba

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08518934B2