O-CYCLOHEXYLHYDROXYLAMINE HYDROCHLORIDE

反应条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (3-Chloro-4-methanesulfonyl-phenyl)-oxo-acetic acid methyl ester (prepared as in Example 1, 1.2 g, 4.34 mmol) was stirred in methanol (9 mL) and warmed in a 70° C. oil bath. O-Cyclohexyl-hydroxylamine hydrochloride (0.811 g, 5.43 mmol) was added. After 2 h, the reaction mixture was allowed to cool and concentrated in vacuo. Purification by flash column chromatography (Merck silica gel 60, 40-63 μm; 20% ethyl acetate/hexanes to 50% ethyl acetate/hexanes) afforded (E)-(3-chloro-4-methanesulfonyl-phenyl)-cyclohexyloxyimino-acetic acid methyl ester as a white solid (552 mg, 34%): H1-NMR (400 MHz, CDCl3) δ=1.34 (3H, m), 1.51 (3H, m), 1.68 (2H, m), 1.96 (2H, m), 3.31 (3H, s), 3.91 (3H, s), 4.39 (1H, m), 7.51 (1H, dd, J=8.1 Hz, J=1.5 Hz), 7.62 (1H, d, J=1.5 Hz), 8.18 (1H, d, J=8.1 Hz). to cool concentrated in vacuo Purification by flash column chromatography (Merck silica gel 60, 40-63 μm; 20% ethyl acetate/hexanes to 50% ethyl acetate/hexanes)

反应条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Hydrazine monohydrate (2.24 mL, 42.20 mmol) was added to a solution of 2-cyclohexyloxy-isoindole-1,3-dione (4.88 g, 21.10 mmol) in a mixture of methanol (12 mL) and methylene chloride (120 mL), and the mixture was stirred at 25° C. for 4 h. The resulting precipitate was filtered off in vacuo, and the filtrate was washed with 5.0 N aqueous ammonium hydroxide (60 mL). The aqueous layer was extracted with methylene chloride (2×25 mL). The combined organic layers were washed with brine, dried over magnesium sulfate and concentrated in vacuo. The residue was dissolved in a 4.0 M solution of hydrochloric acid in dioxane (12 mL) and diluted with diethyl ether (70 mL). The resulting precipitate was collected by filtration in vacuo to afford O-cyclohexyl-hydroxylamine hydrochloride (1.71 g, 45.7%) as a white solid, which was used in the next step without further purification. The resulting precipitate was filtered off in vacuo the filtrate was washed with 5.0 N aqueous ammonium hydroxide (60 mL) The aqueous layer was extracted with methylene chloride (2×25 mL) The combined organic layers were washed with brine dried over magnesium sulfate concentrated in vacuo The residue was dissolved in a 4.0 M solution of hydrochloric acid in dioxane (12 mL) diluted with diethyl ether (70 mL) The resulting precipitate was collected by filtration in vacuo

反应条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Hydrazine monohydrate (2.24 mL, 42.20 mmol) was added to a solution of 2-cyclohexyloxy-isoindole-1,3-dione (4.88 g, 21.10 mmol) in a mixture of methanol (12 mL) and methylene chloride (120 mL), and the mixture was stirred at 25° C. for 4 h. The resulting precipitate was filtered off in vacuo, and the filtrate was washed with 5.0 N aqueous ammonium hydroxide (60 mL). The aqueous layer was extracted with methylene chloride (2×25 mL). The combined organic layers were washed with brine, dried over magnesium sulfate and concentrated in vacuo. The residue was dissolved in a 4.0 M solution of hydrochloric acid in dioxane (12 mL) and diluted with diethyl ether (70 mL). The resulting precipitate was collected by filtration in vacuo to afford O-cyclohexyl-hydroxylamine hydrochloride (1.71 g, 45.7%) as a white solid, which was used in the next step without further purification. The resulting precipitate was filtered off in vacuo the filtrate was washed with 5.0 N aqueous ammonium hydroxide (60 mL) The aqueous layer was extracted with methylene chloride (2×25 mL) The combined organic layers were washed with brine dried over magnesium sulfate concentrated in vacuo The residue was dissolved in a 4.0 M solution of hydrochloric acid in dioxane (12 mL) diluted with diethyl ether (70 mL) The resulting precipitate was collected by filtration in vacuo

反应条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (3-Chloro-4-methanesulfonyl-phenyl)-oxo-acetic acid methyl ester (prepared as in Example 1, 1.2 g, 4.34 mmol) was stirred in methanol (9 mL) and warmed in a 70° C. oil bath. O-Cyclohexyl-hydroxylamine hydrochloride (0.811 g, 5.43 mmol) was added. After 2 h, the reaction mixture was allowed to cool and concentrated in vacuo. Purification by flash column chromatography (Merck silica gel 60, 40-63 μm; 20% ethyl acetate/hexanes to 50% ethyl acetate/hexanes) afforded (E)-(3-chloro-4-methanesulfonyl-phenyl)-cyclohexyloxyimino-acetic acid methyl ester as a white solid (552 mg, 34%): H1-NMR (400 MHz, CDCl3) δ=1.34 (3H, m), 1.51 (3H, m), 1.68 (2H, m), 1.96 (2H, m), 3.31 (3H, s), 3.91 (3H, s), 4.39 (1H, m), 7.51 (1H, dd, J=8.1 Hz, J=1.5 Hz), 7.62 (1H, d, J=1.5 Hz), 8.18 (1H, d, J=8.1 Hz). to cool concentrated in vacuo Purification by flash column chromatography (Merck silica gel 60, 40-63 μm; 20% ethyl acetate/hexanes to 50% ethyl acetate/hexanes)

反应条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Hydrazine monohydrate (2.24 mL, 42.20 mmol) was added to a solution of 2-cyclohexyloxy-isoindole-1,3-dione (4.88 g, 21.10 mmol) in a mixture of methanol (12 mL) and methylene chloride (120 mL), and the mixture was stirred at 25° C. for 4 h. The resulting precipitate was filtered off in vacuo, and the filtrate was washed with 5.0 N aqueous ammonium hydroxide (60 mL). The aqueous layer was extracted with methylene chloride (2×25 mL). The combined organic layers were washed with brine, dried over magnesium sulfate and concentrated in vacuo. The residue was dissolved in a 4.0 M solution of hydrochloric acid in dioxane (12 mL) and diluted with diethyl ether (70 mL). The resulting precipitate was collected by filtration in vacuo to afford O-cyclohexyl-hydroxylamine hydrochloride (1.71 g, 45.7%) as a white solid, which was used in the next step without further purification. The resulting precipitate was filtered off in vacuo the filtrate was washed with 5.0 N aqueous ammonium hydroxide (60 mL) The aqueous layer was extracted with methylene chloride (2×25 mL) The combined organic layers were washed with brine dried over magnesium sulfate concentrated in vacuo The residue was dissolved in a 4.0 M solution of hydrochloric acid in dioxane (12 mL) diluted with diethyl ether (70 mL) The resulting precipitate was collected by filtration in vacuo