3-methylbutanenitrile

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

実験手順: To a solution of 3-methylbutanenitrile (250 mg, 3.0 mmol) and AlCl3 (400 mg, 3.0 mmol) in toluene (6 mL) was added 4-chloroaniline (383 mg, 3.0 mmol). The resulting solution was stirred at reflux for 2 h, diluted with water, and extracted with EtOAc. The aqueous layer was neutralized with saturated NaHCO3 solution and extracted with EtOAc. The combined extracts were dried over MgSO4, filtered, and concentrated. The crude product (364 mg, 58% yield) was used for the next step without purification. at reflux for 2 h extracted with EtOAc extracted with EtOAc The combined extracts were dried over MgSO4 filtered concentrated

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

実験手順: Isovaleronitrile (2.0 g, 24.1 mmol) was dissolved in anhydrous ethanol (48 mL) under an atmosphere of Ar. The solution was cooled to 0° C., saturated with HCl gas, stirred for 6 h, allowed to warm to RT, and stirred for 6 h. The solvent was removed in vacuo to afford ethyl 3-methylbutanimidate hydrochloride (4.0 g, 100%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 12.00 (br s, 1H), 11.09 (br s, 1H), 4.42 (q, J=7.0 Hz, 2H), 2.48-2.47 (m, 2H), 2.02-2.01 (m, 1H), 1.33 (t, J=7.0 Hz, 3H), 0.91 (d, J=6.7 Hz, 6H). stirred for 6 h The solvent was removed in vacuo

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

実験手順: Isovaleronitrile (2.0 g, 24.1 mmol) was dissolved in anhydrous ethanol (48 mL) under an atmosphere of Ar. The solution was cooled to 0° C., saturated with HCl gas, stirred for 6 h, allowed to warm to RT, and stirred for 6 h. The solvent was removed in vacuo to afford ethyl 3-methylbutanimidate hydrochloride (4.0 g, 100%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 12.00 (br s, 1H), 11.09 (br s, 1H), 4.42 (q, J=7.0 Hz, 2H), 2.48-2.47 (m, 2H), 2.02-2.01 (m, 1H), 1.33 (t, J=7.0 Hz, 3H), 0.91 (d, J=6.7 Hz, 6H). stirred for 6 h The solvent was removed in vacuo

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of dimethyl 2-aminoterephthalate (3.0 g, 14.4 mmol), 3-methylbutanenitrile (1.2 g, 14.4 mmol), and saturated HCl solution in dioxane (20 mL) in sealed tube was stirred at 100° C. overnight. After it was cooled to room temperature, the reaction mixture was poured into water (50 mL) and extracted with ethyl acetate (3×20 mL). The combined organic layer was concentrated and the residue was purified by silica gel chromatography give the desired product. MS (ESI): 260 (MH+). After it was cooled to room temperature extracted with ethyl acetate (3×20 mL) The combined organic layer was concentrated the residue was purified by silica gel chromatography

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

実験手順: Isovaleronitrile (14.1 g, 170 mmol) and hydroxylamine hydrochloride (60 g, 850 mmol) were heated under reflux in methanol (300 ml) and water (300 ml) for 5 hours. The reaction mixture was cooled to room temperature, solid sodium carbonate added cautiously and the mixture filtered. The filtrate was concentrated under reduced pressure and extracted with dichloromethane (3×). The combined organic solutions were washed with water and brine, dried (MgSO4), filtered and concentrated under reduced pressure to give a white solid, 15.5 g. In a separate flask 1-(tert-butoxycarbonyl)4-piperidinecarboxylic acid (250 mg, 1.09 mmol) in dichloromethane (5 ml) was treated with diisopropylethylamine (0.28 ml, 2.70 mmol). Bis(tetramethylene)fluoroformamidinium hexafluorophosphate (413 mg, 1.31 mmol) in dichloromethane (5 ml) was added to the solution and stirred at room temperature for 1 hour. A portion of the intermediate white solid (150 mg, 1.31 mmol) and diisopropylethylamine (0.23 ml, 1.09 mmol) in dichloromethane (2 ml) were added, the resulting solution was stirred at room temperature for 16 hours, then heated to 50° C. to concentrate the solution. Dioxane (10 ml) was added and the solution heated to 120° C. for 3 hours. The reaction was cooled to room temperature, diluted with ethyl acetate, washed with saturated aqueous sodium bicarbonate solution and 1M citric acid solution. The combined organic solutions were dried (MgSO4), filtered and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel, using ethyl acetate: pentane (25:75) as eluant to afford the title compound as an oil, 209 mg. the mixture filtered The filtrate was concentrated under reduced pressure extracted with dichloromethane (3×) The combined organic solutions were washed with water and brine dried (MgSO4) filtered concentrated under reduced pressure to give a white solid, 15.5 g the resulting solution was stirred at room temperature for 16 hours heated to 50° C. to concentrate the solution Dioxane (10 ml) was added the solution heated to 120° C. for 3 hours The reaction was cooled to room temperature diluted with ethyl acetate washed with saturated aqueous sodium bicarbonate solution and 1M citric acid solution The combined organic solutions were dried (MgSO4) filtered evaporated under reduced pressure The residue was purified by column chromatography on silica gel

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

実験手順: To a solution of 3-methylbutanenitrile (250 mg, 3.0 mmol) and AlCl3 (400 mg, 3.0 mmol) in toluene (6 mL) was added 4-chloroaniline (383 mg, 3.0 mmol). The resulting solution was stirred at reflux for 2 h, diluted with water, and extracted with EtOAc. The aqueous layer was neutralized with saturated NaHCO3 solution and extracted with EtOAc. The combined extracts were dried over MgSO4, filtered, and concentrated. The crude product (364 mg, 58% yield) was used for the next step without purification. at reflux for 2 h extracted with EtOAc extracted with EtOAc The combined extracts were dried over MgSO4 filtered concentrated

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

実験手順: Isovaleronitrile (2.0 g, 24.1 mmol) was dissolved in anhydrous ethanol (48 mL) under an atmosphere of Ar. The solution was cooled to 0° C., saturated with HCl gas, stirred for 6 h, allowed to warm to RT, and stirred for 6 h. The solvent was removed in vacuo to afford ethyl 3-methylbutanimidate hydrochloride (4.0 g, 100%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 12.00 (br s, 1H), 11.09 (br s, 1H), 4.42 (q, J=7.0 Hz, 2H), 2.48-2.47 (m, 2H), 2.02-2.01 (m, 1H), 1.33 (t, J=7.0 Hz, 3H), 0.91 (d, J=6.7 Hz, 6H). stirred for 6 h The solvent was removed in vacuo