O-(4-chlorophenyl)hydroxylamine;hydrochloride

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of N-(2-acetyl-5-trifluoromethylphenyl)trifluoromethanesulfonamide 35 (250 g, 0.75 mmol), O-(4-chlorophenyl)hydroxylamine hydrochloride (148 mg, 0.82 mmol) and anhydrous NaOAc (67 mg, 0.82 mmol) in EtOH (15 mL) was stirred for 20 hours at RT. The reaction mixture was concentrated under vacuum, the residue filtered through a pad of silica (eluting with CH2Cl2) and the solvent removed under reduced pressure. The residue was purified by recrystallization from CH2Cl2/PE to afford N-{2-[1-(4-chlorophenoxyimino)ethyl]-5-trifluoromethylphenyl}trifluoromethanesulfonamide 199 (310 mg, 90%), as a pale yellow solid. M.p. 89-90° C. 1H n.m.r. (200 MHz, CDCl3) δ 11.41, br s, 1H; 8.02, s, 1H; 7.76, d, J=8.6 Hz, 1H; 7.56, m, 1H; 7.36, d, J=9.2 Hz, 2H; 7.12, d, J=9.2 Hz, 2H; 2.60, s, 3H. The reaction mixture was concentrated under vacuum the residue filtered through a pad of silica (eluting with CH2Cl2) the solvent removed under reduced pressure The residue was purified by recrystallization from CH2Cl2/PE

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of N-(4-chloro-2-isobutyrylphenyl)trifluoromethanesulfonamide 31B (244 mg, 1.11 mmol), O-(4-Chlorophenyl)hydroxylamine hydrochloride (200 mg, 0.91 mmol) and anhydrous NaOAc (91 mg, 1.11 mmol) in EtOH (10 mL) was stirred for 48 h at RT. The reaction mixture was concentrated under vacuum, and the residue purified by column chromatography (eluting with CH2Cl2/PE, 3:7) to afford N-{4-chloro-2-[1-(4-chlorophenoxyimino)-2-methylpropyl]phenyl}trifluoromethanesulfonamide 215 (80 mg, 24%), as an orange oil. 1H n.m.r. (200 MHz, CDCl3) δ 7.56, d, J=8.8 Hz, 1H; 7.45, dd, J=2.4 and 8.8 Hz, 1H; 7.27, d, J=9.0 Hz, 2H; 7.23, d, J=2.4 Hz, 1H; 7.07, d, J=9.0 Hz, 2H; 2.94, m,1H; 1.37, s, 3H; 1.19, s, 3H. The reaction mixture was concentrated under vacuum the residue purified by column chromatography (eluting with CH2Cl2/PE, 3:7)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of N-(4-chloro-2-isobutyrylphenyl)trifluoromethanesulfonamide 31B (244 mg, 1.11 mmol), O-(4-Chlorophenyl)hydroxylamine hydrochloride (200 mg, 0.91 mmol) and anhydrous NaOAc (91 mg, 1.11 mmol) in EtOH (10 mL) was stirred for 48 h at RT. The reaction mixture was concentrated under vacuum, and the residue purified by column chromatography (eluting with CH2Cl2/PE, 3:7) to afford N-{4-chloro-2-[1-(4-chlorophenoxyimino)-2-methylpropyl]phenyl}trifluoromethanesulfonamide 215 (80 mg, 24%), as an orange oil. 1H n.m.r. (200 MHz, CDCl3) δ 7.56, d, J=8.8 Hz, 1H; 7.45, dd, J=2.4 and 8.8 Hz, 1H; 7.27, d, J=9.0 Hz, 2H; 7.23, d, J=2.4 Hz, 1H; 7.07, d, J=9.0 Hz, 2H; 2.94, m,1H; 1.37, s, 3H; 1.19, s, 3H. The reaction mixture was concentrated under vacuum the residue purified by column chromatography (eluting with CH2Cl2/PE, 3:7)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of N-[4-chloro-2-(2,2-dimethylpropionyl)phenyl]trifluoromethanesulfonamide 29C (300 mg, 0.87 mmol), O-(4-chlorophenyl)hydroxylamine hydrochloride (173 mg, 0.96 mmol) and anhydrous NaOAc (80 mg, 0.96 mmol) in EtOH (20 mL) was stirred for 40 hours at RT. The reaction mixture was concentrated under vacuum, the residue filtered through a pad of silica (eluting with CH2Cl2/PE, 3:7) and the solvent removed under reduced pressure. The residue was purified by recrystallization from CH2Cl2/PE to afford N-{4-chloro-2-[1-(4-chlorophenoxyimino)butyl]phenyl}trifluoromethanesulfonamide 182 (40 mg, 10%), as a yellow solid. M.p. 69-70° C. 1H n.m.r. (200 MHz, CDCl3) δ 7.52, d, J=8.8 Hz, 1H; 7.43, dd, J=2.2 and 8.8 Hz, 1H; 7.25, d, J=9.2 Hz, 2H; 7.18, d, J=2.2 Hz, 1H; 7.01, d, J=9.2 Hz, 2H; 6.43, br s, 1H; 1.33, s, 9H. The reaction mixture was concentrated under vacuum the residue filtered through a pad of silica (eluting with CH2Cl2/PE, 3:7) the solvent removed under reduced pressure The residue was purified by recrystallization from CH2Cl2/PE

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of N-(2-butyryl-4-chlorophenyl)trifluoromethanesulfonamide 29A (333 mg, 1.0 mmol), O-(4-chlorophenyl)hydroxylamine hydrochloride (200 mg, 1.10 mmol) and anhydrous NaOAc (91 mg, 1.10 mmol) in EtOH (30 mL) was stirred for 15 hours at RT. The reaction mixture was concentrated under vacuum, the residue filtered through a pad of silica (eluting with CH2Cl2/PE, 1:4) and the solvent removed under reduced pressure. The residue was purified by radial thin layer chromatography (eluting with CH2Cl2/PE, 1:19 to 3:7) to afford N-{4-chloro-2-[1-(4-chlorophenoxyimino)butyl]phenyl}trifluoromethanesulfonamide 166 (283 mg, 62%), as a yellow solid. M.p. 62.5-64.5° C. 1H n.m.r. (200 MHz, CDCl3) δ 11.27, br s, 1H; 7.72, d, J=8.8 Hz, 1H; 7.57, d, J=2.4 Hz, 1H; 7.41, dd, J=2.4 and 8.8 Hz, 1H; 7.35, d, J=8.8 Hz, 2H; 7.11, d, J=8.8 Hz, 2H; 2.98, m, 2H; 1.71, sextet, 2H; 1.09, t, J=7.4 Hz, 3H. The reaction mixture was concentrated under vacuum the residue filtered through a pad of silica (eluting with CH2Cl2/PE, 1:4) the solvent removed under reduced pressure The residue was purified by radial thin layer chromatography (eluting with CH2Cl2/PE, 1:19 to 3:7)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N,N-Dimethylethylenediamine (82 μL, 0.75 mmol) was added to a suspension of O-(4-chlorophenyl)hydroxylamine hydrochloride (141 mg, 0.51 mmol) in EtOH (15 mL), and the reaction allowed to stir at RT for 15 hours. Glacial acetic acid (3 mL) was then added to adjust the mixture to ca. pH 4 followed by a solution of N-(2-benzoyl-4-chlorophenyl)trifluoromethanesulfonamide 25 (170 mg, 0.47 mmol) in EtOH (5 mL), and the reaction stirred for 63 hours at RT. The reaction mixture was concentrated under vacuum, and the residue dissolved in CH2Cl2 (50 mL), washed with water (twice), brine, dried over MgSO4 and the solvent evaporated under reduced pressure. The residue was filtered through a pad of silica (eluting with CH2Cl2/PE, 3:7) and purified by radial thin layer chromatography (eluting with CH2Cl2/PE, 1:19 to 1:4) to afford N-{4-chloro-2-[(4-chlorophenoxyimino)phenylmethyl]phenyl}trifluoromethanesulfonamide 164 (140 mg, 61%), as a orange-brown solid. M.p. 86-87° C. 1H n.m.r. (200 MHz, CDCl3) δ 10.99, br s, 1H; 7.73, d, J=8.8 Hz, 1H; 7.54, m, 3H; 7.43-7.27, m, 5H; 7.07, m, 1H; 7.01, m, 2H. O-(4-Chlorophenyl)hydroxylamine hydrochloride was prepared by the procedure described in Example 2C. the reaction stirred for 63 hours at RT The reaction mixture was concentrated under vacuum the residue dissolved in CH2Cl2 (50 mL) washed with water (twice), brine dried over MgSO4 the solvent evaporated under reduced pressure The residue was filtered through a pad of silica (eluting with CH2Cl2/PE, 3:7) purified by radial thin layer chromatography (eluting with CH2Cl2/PE, 1:19 to 1:4)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of N-(4-chloro-2-propionylphenyl)trifluoromethanesulfonamide 22 (450 mg, 1.43 mmol), O-(4-chlorophenyl)hydroxylamine hydrochloride (257 mg, 1.43 mmol) and anhydrous NaOAc (125 mg, 1.52 mmol) in EtOH (23 mL) was stirred for 15 h at RT. The reaction mixture was concentrated under vacuum and the residue filtered through a pad of silica (eluting with CH2Cl2/PE, 3:2). The residue was purified by radial thin layer chromatography (eluting with CH2Cl2iPE, 1:5) to afford N-{4-chloro-2-[1-(4-chlorophenoxyimino)propyl]phenyl}trifluoromethanesulfonamide 128 (455 mg, 72%), as a yellow solid. M.p. 87-88° C. 1H n.m.r. (200 MHz, CDCl3) δ 11.18, br s, 1H; 7.71, d, J=8.8 Hz, 1H; 7.58, d, J=2.6 Hz, 1H; 7.41, dd, J=2.6 and 8.8 Hz, 1H; 7.35, d, J=8.8 Hz, 2H; 7.11, d, J=8.8 Hz, 2H; 3.02, q, J=7.6 Hz, 2H; 1.30, t, J=7.6 Hz, 3H. The reaction mixture was concentrated under vacuum the residue filtered through a pad of silica (eluting with CH2Cl2/PE, 3:2) The residue was purified by radial thin layer chromatography (eluting with CH2Cl2iPE, 1:5)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of N-(2-acetyl-5-trifluoromethylphenyl)trifluoromethanesulfonamide 35 (250 mg, 0.75 mmol), O-(4-chlorophenyl)hydroxylamine hydrochloride (148 mg, 0.82 mmol) and anhydrous NaOAc (67 mg, 0.82 mmol) in EtOH (15 mL) was stirred for 20 hours at RT. The reaction mixture was concentrated under vacuum, the residue filtered through a pad of silica (eluting with CH2Cl2) and the solvent removed under reduced pressure. The residue was purified by recrystallization from CH2Cl2/PE to afford N-{2-[1-(4-chlorophenoxyimino)ethyl]-5-trifluoromethylphenyl}trifluoromethanesulfonamide 199 (310 mg, 90%), as a pale yellow solid. M.p. 89-90° C. 1H n.m.r. (200 MHz, CDCl3) δ 11.41, br s, 1H, 8.02, s, 1H, 7.76, d, J=8.6 Hz, 1H, 7.56, m, 1H, 7.36, d, J=9.2 Hz, 2H, 7.12, d, J=9.2 Hz, 2H, 2.60, s, 3H. The reaction mixture was concentrated under vacuum the residue filtered through a pad of silica (eluting with CH2Cl2) the solvent removed under reduced pressure The residue was purified by recrystallization from CH2Cl2/PE

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of N-(2-acetyl-5-trifluoromethylphenyl)trifluoromethanesulfonamide 35 (250 mg, 0.75 mmol), O-(4-chlorophenyl)hydroxylamine hydrochloride (148 mg, 0.82 mmol) and anhydrous NaOAc (67 mg, 0.82 mmol) in EtOH (15 mL) was stirred for 20 hours at RT. The reaction mixture was concentrated under vacuum, the residue filtered through a pad of silica (eluting with CH2Cl2) and the solvent removed under reduced pressure. The residue was purified by recrystallization from CH2Cl2/PE to afford N-{2-[1-(4-chlorophenoxyimino)ethyl]-5-trifluoromethylphenyl}trifluoromethanesulfonamide 199 (310 mg, 90%), as a pale yellow solid. M.p. 89-90° C. 1H n.m.r. (200 MHz, CDCl3) δ 11.41, br s, 1H, 8.02, s, 1H, 7.76, d, J=8.6 Hz, 1H, 7.56, m, 1H, 7.36, d, J=9.2 Hz, 2H, 7.12, d, J=9.2 Hz, 2H, 2.60, s, 3H. The reaction mixture was concentrated under vacuum the residue filtered through a pad of silica (eluting with CH2Cl2) the solvent removed under reduced pressure The residue was purified by recrystallization from CH2Cl2/PE

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of N-(4-chloro-2-isobutyrylphenyl)trifluoromethanesulfonamide 31B (244 mg, 1.11 mmol), O-(4-Chlorophenyl)hydroxylamine hydrochloride (200 mg, 0.91 mmol) and anhydrous NaOAc (91 mg, 1.11 mmol) in EtOH (10 mL) was stirred for 48 h at RT. The reaction mixture was concentrated under vacuum, and the residue purified by column chromatography (eluting with CH2Cl2/PE, 3:7) to afford N-{4-chloro-2-[1-(4-chlorophenoxyimino)-2-methylpropyl]phenyl}trifluoromethanesulfonamide 215 (80 mg, 24%), as an orange oil. 1H n.m.r. (200 MHz, CDCl3) δ 7.56, d, J=8.8 Hz, 1H; 7.45, dd, J=2.4 and 8.8 Hz, 1H, 7.27, d, J==90 Hz, 2H, 7.23, d, J=2.4 Hz, 1H, 7.07, d, J=9.0 Hz, 2H, 2.94, m, 1H, 1.37, s, 3H, 1.19, s, 3H. The reaction mixture was concentrated under vacuum the residue purified by column chromatography (eluting with CH2Cl2/PE, 3:7)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of N-[4-chloro-2-(2,2-dimethylpropionyl)phenyl]trifluoromethanesulfonamide 29C (300 mg, 0.87 mmol), O-(4-chlorophenyl)hydroxylamine hydrochloride (173 mg, 0.96 mmol) and anhydrous NaOAc (80 mg, 0.96 mmol) in EtOH (20 mL) was stirred for 40 hours at RT. The reaction mixture was concentrated under vacuum, the residue filtered through a pad of silica (eluting with CH2Cl2/PE, 3:7) and the solvent removed under reduced pressure. The residue was purified by recrystallization from CH2Cl2/PE to afford N-{4-chloro-2-[1-(4-chlorophenoxyimino)butyl]phenyl}trifluoromethanesulfonamide 182 (40 mg, 10%), as a yellow solid. M.p. 69-70° C. 1H n.m.r. (200 MHz, CDCl3) δ 7.52, d, J=8.8 Hz, 1H, 7.43, dd, J=2.2 and 8.8 Hz, 1H, 7.25, d, J=9.2 Hz, 2H, 7.18, d, J=2.2 Hz, 1H, 7.01, d, J=9.2 Hz, 2H, 6.43, br s, 1H, 1.33, s, 9H. The reaction mixture was concentrated under vacuum the residue filtered through a pad of silica (eluting with CH2Cl2/PE, 3:7) the solvent removed under reduced pressure The residue was purified by recrystallization from CH2Cl2/PE

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of N-[4-chloro-2-(2,2-dimethylpropionyl)phenyl]trifluoromethanesulfonamide 29C (300 mg, 0.87 mmol), O-(4-chlorophenyl)hydroxylamine hydrochloride (173 mg, 0.96 mmol) and anhydrous NaOAc (80 mg, 0.96 mmol) in EtOH (20 mL) was stirred for 40 hours at RT. The reaction mixture was concentrated under vacuum, the residue filtered through a pad of silica (eluting with CH2Cl2/PE, 3:7) and the solvent removed under reduced pressure. The residue was purified by recrystallization from CH2Cl2/PE to afford N-{4-chloro-2-[1-(4-chlorophenoxyimino)butyl]phenyl}trifluoromethanesulfonamide 182 (40 mg, 10%), as a yellow solid. M.p. 69-70° C. 1H n.m.r. (200 MHz, CDCl3) δ 7.52, d, J=8.8 Hz, 1H, 7.43, dd, J=2.2 and 8.8 Hz, 1H, 7.25, d, J=9.2 Hz, 2H, 7.18, d, J=2.2 Hz, 1H, 7.01, d, J=9.2 Hz, 2H, 6.43, br s, 1H, 1.33, s, 9H. The reaction mixture was concentrated under vacuum the residue filtered through a pad of silica (eluting with CH2Cl2/PE, 3:7) the solvent removed under reduced pressure The residue was purified by recrystallization from CH2Cl2/PE