N-phenylpropanamide

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: iPr2EtN (4.72 mL, 27.1 mmol) was added to a solution of (4-benzyl-1,4-oxazepan-2-ylmethyl) phenyl amine (80) (27.1 mmol) in CH2Cl2. The solution was cooled to 0° C. in an ice bath, then propionyl chloride (5.17 mL, 59.6 mmol) was added dropwise. The reaction was allowed to warm slowly to room temperature, with stirring, overnight. CH2Cl2 and 10% aqueous NaOH was added. The organic layer was removed and the aqueous layer extracted with CH2Cl2 (2×). The organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The resulting oily residue was purified by silica gel chromatography (97:1:2::Hexanes:CH2Cl2:2N NH3 in EtOH) to obtain 4-benzyl-1,4-oxazepan-2-ylmethyl)-N-phenylpropionamide (81) as a pale yellow oil. 1H NMR (CDCl3, ppm) 7.36-7.19 (8H, m), 6.94 (2H, broad d, J=6.5 Hz), 3.89-3.38 (5H, m), 3.65 (1H, d, J=13.3 Hz), 3.54 (1H, d, J=13.3 Hz), 2.88-2.75 (2H, m), 2.55 (1H, ddd, J=12.5, 8.9, 4.2 Hz), 2.34 (1H, dd, J=13.5, 8.9 Hz), 1.98-1.68 (4H, m), 0.98 (3H, t, J=7.5 Hz). 13C NMR (CDCl3) 174.05, 143.19, 139.64, 129.60, 129.15, 128.46, 128.35, 127.79, 127.10, 76.80, 67.25, 62.61, 59.05, 54.43, 51.64, 30.42, 27.91, 9.70 ppm. LRMS: 352.72. to warm slowly to room temperature The organic layer was removed the aqueous layer extracted with CH2Cl2 (2×) The organic extracts were dried with sodium sulfate filtered concentrated in vacuo The resulting oily residue was purified by silica gel chromatography (97:1:2::Hexanes:CH2Cl2:2N NH3 in EtOH)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-phenylpropionamide(7.46 g, 0.05 mol) and pyridine(13.8 g, 0.18 mol) were dissolved in dichloromethane(300 g) , and the mixture was cooled to 0° C. And then phosphorus oxychloride(8.43 g, 0.05 mol) was added dropwise thereto for 2 hours, and then the mixture was stirred at room temperature (20° C.) for 2 hours to produce N-phenylpropionimidoylchloride.

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-phenylpropionamide(149.2 g, 1.0 mol) and pyridine(261.0 g, 3.3 mol) were dissolved in dichloromethane(300 g), and the mixture was cooled to 0° C. Phosphorus oxychloride(168.7 g, 1.1 mol) was added dropwise thereto for 2 hours, and then the mixture was stirred at room temperature (20° C.) for 2 hours to produce N-phenylpropionimidoylchloride.

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-phenylpropionamide(149.2 g, 1.0 mol) and pyridine(261.0 g, 3.3 mol) were dissolved in dichloromethane(300 g), and the mixture was cooled to 0° C. Phosphorus oxychloride(168.7 g, 1.1 mol) was added dropwise thereto for 2 hours, and then the mixture was stirred at room temperature (20° C.) for 2 hours to produce N-phenylpropionimidoylchloride.

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: iPr2EtN (4.72 mL, 27.1 mmol) was added to a solution of (4-benzyl-1,4-oxazepan-2-ylmethyl)phenyl amine (80) (27.1 mmol) in CH2Cl2. The solution was cooled to 0° C. in an ice bath, then propionyl chloride (5.17 mL, 59.6 mmol) was added dropwise. The reaction was allowed to warm slowly to room temperature, with stirring, overnight. CH2Cl2 and 10% aqueous NaOH was added. The organic layer was removed and the aqueous layer extracted with CH2Cl2 (2×). The organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The resulting oily residue was purified by silica gel chromatography (97:1:2::Hexanes:CH2Cl2:2N NH3 in EtOH) to obtain 4-benzyl-1,4-oxazepan-2-ylmethyl)-N-phenylpropionamide (81) as a pale yellow oil. 1H NMR (CDCl3, ppm) 7.36-7.19 (8H, m), 6.94 (2H, broad d, J=6.5 Hz), 3.89-3.38 (5H, m), 3.65 (1H, d, J=13.3 Hz), 3.54 (1H, d, J=13.3 Hz), 2.88-2.75 (2H, m), 2.55 (1H, ddd, J=12.5, 8.9, 4.2 Hz), 2.34 (1H, dd, J=13.5, 8.9 Hz), 1.98-1.68 (4H, m), 0.98 (3H, t, J=7.5 Hz). 13C NMR (CDCl3) 174.05, 143.19, 139.64, 129.60, 129.15, 128.46, 128.35, 127.79, 127.10, 76.80, 67.25, 62.61, 59.05, 54.43, 51.64, 30.42, 27.91, 9.70 ppm. LRMS: 352.72. to warm slowly to room temperature The organic layer was removed the aqueous layer extracted with CH2Cl2 (2×) The organic extracts were dried with sodium sulfate filtered concentrated in vacuo The resulting oily residue was purified by silica gel chromatography (97:1:2::Hexanes:CH2Cl2:2N NH3 in EtOH)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: iPr2EtN (4.72 mL, 27.1 mmol) was added to a solution of (4-benzyl-1,4-oxazepan-2-ylmethyl)phenyl amine (80) (27.1 mmol) in CH2Cl2. The solution was cooled to 0° C. in an ice bath, then propionyl chloride (5.17 mL, 59.6 mmol) was added dropwise. The reaction was allowed to warm slowly to room temperature, with stirring, overnight. CH2Cl2 and 10% aqueous NaOH was added. The organic layer was removed and the aqueous layer extracted with CH2Cl2 (2×). The organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The resulting oily residue was purified by silica gel chromatography (97:1:2::Hexanes:CH2Cl2:2N NH3 in EtOH) to obtain 4-benzyl-1,4-oxazepan-2-ylmethyl)-N-phenylpropionamide (81) as a pale yellow oil. 1H NMR (CDCl3, ppm) 7.36-7.19 (8H, m), 6.94 (2H, broad d, J=6.5 Hz), 3.89-3.38 (5H, m), 3.65 (1H, d, J=13.3 Hz), 3.54 (1H, d, J=13.3 Hz), 2.88-2.75 (2H, m), 2.55 (1H, ddd, J=12.5, 8.9, 4.2 Hz), 2.34 (1H, dd, J=13.5, 8.9 Hz), 1.98-1.68 (4H, m), 0.98 (3H, t, J=7.5 Hz). 13C NMR (CDCl3) 174.05, 143.19, 139.64, 129.60, 129.15, 128.46, 128.35, 127.79, 127.10, 76.80, 67.25, 62.61, 59.05, 54.43, 51.64, 30.42, 27.91, 9.70 ppm. LRMS: 352.72. to warm slowly to room temperature The organic layer was removed the aqueous layer extracted with CH2Cl2 (2×) The organic extracts were dried with sodium sulfate filtered concentrated in vacuo The resulting oily residue was purified by silica gel chromatography (97:1:2::Hexanes:CH2Cl2:2N NH3 in EtOH)

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: Using 2-methylacetanilide (4.48 g) and 2-bromo-3-methylpyridine (10.3 g), a reaction was made in the same manner as in 1) of Production Example 14. The subsequent purification by silica gel column chromatography (developing solvent, ethyl acetate: hexane=1:3) produced 2-methyl-N-(3-methyl-2-pyridyl)acetanilide (7.2 g, crude product) as a pale brown oil. The subsequent purification by silica gel column chromatography (developing solvent, ethyl acetate: hexane=1:3)

反応条件: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2-methylacetanilide (4.5 g), iodobenzene (6.8 ml), potassium carbonate (8.3 g), and copper iodide (574 mg) was stirred overnight at 150° C. After the mixture was allowed to cool, water and ethyl acetate were added thereto, and the mixture was further stirred. The mixture was then filtered with celite. Filtrate was collected, and an aqueous phase was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over sodium sulfate. The resulting solution was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (developing solvent, ethyl acetate:hexane=1:2.5) to obtain 2-methyl-N-phenylacetanilide (4.96 g; yield, 73%) as a light brown oil. to cool The mixture was then filtered with celite Filtrate was collected an aqueous phase was extracted with ethyl acetate The extract was washed with water and saturated brine dried over sodium sulfate The resulting solution was filtered the filtrate was concentrated under reduced pressure The residue was purified by silica gel column chromatography (developing solvent, ethyl acetate:hexane=1:2.5)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-phenylpropionamide(7.46 g, 0.05 mol) and pyridine(13.8 g, 0.18 mol) were dissolved in dichloromethane(300 g), and the mixture was cooled to 0° C. And then phosphorus oxychloride(8.43 g, 0.05 mol) was added dropwise thereto for 2 hours, and then the mixture was stirred at room temperature (20° C.) for 2 hours to produce N-phenylpropionimidoylchloride.

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-phenylpropionamide(149.2 g, 1.0 mol) and pyridine(261.0 g, 3.3 mol) were dissolved in dichloromethane(300 g), and the mixture was cooled to 0° C. Phosphorus oxychloride(168.7 g, 1.1 mol) was added dropwise thereto for 2 hours, and then the mixture was stirred at room temperature (20° C.) for 2 hours to produce N-phenylpropionimidoylchloride.