1-benzyl-4-methyl-1,4lambda5-azaphosphinane 4-oxide

反応条件: temp:0.00; pressure:0.00; stir:

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: A solution of methyl divinyl phosphine oxide (1.16 g, 10.0 mmol) and benzylamine (1.20 mL, 11.0 mmol) in 1:1 THF/water (25 mL) was heated at reflux for 16 h. The reaction mixture was concentrated in vacuo and the residue was purified by silica gel chromatography (0-10% 7N ammonia in methanol:dichloromethane) to afford 1-benzyl-4-methyl-[1,4]azaphosphinane-4-oxide as a white solid (1.57 g, 70% yield). at reflux for 16 h The reaction mixture was concentrated in vacuo the residue was purified by silica gel chromatography (0-10% 7N ammonia in methanol:dichloromethane)

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

実験手順: A solution of methyl divinyl phosphine oxide (1.16 g, 10.0 mmol) and benzylamine (1.20 mL, 11.0 mmol) in 1:1 THF/water (25 mL) was heated at reflux for 16 h. The reaction mixture was concentrated in vacuo and the residue was purified by silica gel chromatography (0-10% 7N ammonia in methanol:dichloromethane) to afford 1-benzyl-4-methyl-[1,4]azaphosphinane-4-oxide as a white solid (1.57 g, 70% yield). at reflux for 16 h The reaction mixture was concentrated in vacuo the residue was purified by silica gel chromatography (0-10% 7N ammonia in methanol:dichloromethane)

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

実験手順: A solution of methyl divinyl phosphine oxide (1.16 g, 10.0 mmol) and benzylamine (1.20 mL, 11.0 mmol) in 1:1 THF/water (25 mL) was heated at reflux for 16 h. The reaction mixture was concentrated in vacuo and the residue was purified by silica gel chromatography (0-10% 7N ammonia in methanol:dichloromethane) to afford 1-benzyl-4-methyl-[1,4]azaphosphinane-4-oxide as a white solid (1.57 g, 70% yield). at reflux for 16 h The reaction mixture was concentrated in vacuo the residue was purified by silica gel chromatography (0-10% 7N ammonia in methanol:dichloromethane)

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

実験手順: A solution of methyl divinyl phosphine oxide (1.16 g, 10.0 mmol) and benzylamine (1.20 mL, 11.0 mmol) in 1:1 THF/water (25 mL) was heated at reflux for 16 h. The reaction mixture was concentrated in vacuo and the residue was purified by silica gel chromatography (0-10% 7N ammonia in methanol:dichloromethane) to afford 1-benzyl-4-methyl-[1,4]azaphosphinane-4-oxide as a white solid (1.57 g, 70% yield). at reflux for 16 h The reaction mixture was concentrated in vacuo the residue was purified by silica gel chromatography (0-10% 7N ammonia in methanol:dichloromethane)

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

実験手順: A solution of 1-benzyl-4-methyl-1,4-azaphosphinane 4-oxide (5 g) in methanol (50 mL) and 3 M HCl (10 mL) with palladium on carbon (10%, 1.0 g) was hydrogenated on a Parr shaker for 24 hours at 60 psi. The mixture was filtered through Celite and all solvents were removed under reduced pressure to give a white crystalline solid, which was used without further purification. The mixture was filtered through Celite all solvents were removed under reduced pressure to give a white crystalline solid, which was used without further purification

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

実験手順: To a vigorously stirred solution of methylphosphonic dichloride (6.65 g, 50 mmol) in THF (100 mL) at −78° C. was added vinylmagnesium chloride (1.6 M in THF, 66 mL, 105 mmol) dropwisely over 30 min. After the addition is completed, the reaction mixture was warmed to 0° C. over 1 hour, and to it was added benzylamine (6.43 g, 60 mmol) and methanol (100 mL). The reaction mixture was then refluxed for 36 hours. After cooled to room temperature, the reaction mixture was poured into a separation funnel containing saturated aqueous ammonium chloride (100 mL), ethyl acetate (200 mL) and water (100 mL). The organic layer was separated, and the aqueous layer was extracted with methylene chloride (100 mL) twice. The combined organic layer and extracts were dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by flash chromatography, eluting with 20% methanol in dichloromethane to give the desired product as white crystalline solid (5.69 g, 51%). LCMS ESI(+) m/z: 224 (M+1). After the addition The reaction mixture was then refluxed for 36 hours After cooled to room temperature the reaction mixture was poured into a separation funnel The organic layer was separated the aqueous layer was extracted with methylene chloride (100 mL) twice The combined organic layer and extracts were dried over anhydrous magnesium sulfate filtered concentrated The residue was purified by flash chromatography eluting with 20% methanol in dichloromethane

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

実験手順: To a vigorously stirred solution of methylphosphonic dichloride (6.65 g, 50 mmol) in THF (100 mL) at −78° C. was added vinylmagnesium chloride (1.6 M in THF, 66 mL, 105 mmol) dropwisely over 30 min. After the addition is completed, the reaction mixture was warmed to 0° C. over 1 hour, and to it was added benzylamine (6.43 g, 60 mmol) and methanol (100 mL). The reaction mixture was then refluxed for 36 hours. After cooled to room temperature, the reaction mixture was poured into a separation funnel containing saturated aqueous ammonium chloride (100 mL), ethyl acetate (200 mL) and water (100 mL). The organic layer was separated, and the aqueous layer was extracted with methylene chloride (100 mL) twice. The combined organic layer and extracts were dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by flash chromatography, eluting with 20% methanol in dichloromethane to give the desired product as white crystalline solid (5.69 g, 51%). LCMS ESI(+) m/z: 224 (M+1). After the addition The reaction mixture was then refluxed for 36 hours After cooled to room temperature the reaction mixture was poured into a separation funnel The organic layer was separated the aqueous layer was extracted with methylene chloride (100 mL) twice The combined organic layer and extracts were dried over anhydrous magnesium sulfate filtered concentrated The residue was purified by flash chromatography eluting with 20% methanol in dichloromethane

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

実験手順: 1-Benzyl-4-methyl-[1,4]azaphosphinane 4-oxide was dissolved in ethanol (100 mL). 1 M HCl (100 mL) was added, along with palladium on carbon (10%, 2.6 g). The mixture was hydrogenated on a Parr shaker for 4 hours at 50 psi. The mixture was filtered through Celite and all solvents were removed under reduced pressure. The product was triturated in hot ethanol (50 mL) and cooled, and the solution was diluted with ether (300 mL). The white crystalline solid was filtered, washed with ether (2×50 mL), hexane (2×50 mL), and dried in vacuo. 4-methyl-[1,4]azaphosphinane 4-oxide hydrochloride was obtained as a white crystalline solid (9.46 g, 94%). 1H NMR (400 MHz, DMSO) δ 3.07 (m, 2H); 2.68 (m, 2H); 1.78 (m, 2H); 1.61 (m, 2H), 1.39 (3H, d, JH-C—P=13.6 Hz.); 31P NMR: δ 29 ppm; ESMS (m/z): (M+1)+ found, 134. The mixture was filtered through Celite all solvents were removed under reduced pressure The product was triturated in hot ethanol (50 mL) cooled the solution was diluted with ether (300 mL) The white crystalline solid was filtered washed with ether (2×50 mL), hexane (2×50 mL) dried in vacuo

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

実験手順: 1-Benzyl-4-methyl-[1,4]azaphosphinane 4-oxide was dissolved in ethanol (100 mL). 1 M HCl (100 mL) was added, along with palladium on carbon (10%, 2.6 g). The mixture was hydrogenated on a Parr shaker for 4 hours at 50 psi. The mixture was filtered through Celite and all solvents were removed under reduced pressure. The product was triturated in hot ethanol (50 mL) and cooled, and the solution was diluted with ether (300 mL). The white crystalline solid was filtered, washed with ether (2×50 mL), hexane (2×50 mL), and dried in vacuo. 4-methyl-[1,4]azaphosphinane 4-oxide hydrochloride was obtained as a white crystalline solid (9.46 g, 94%). 1H NMR (400 MHz, DMSO) δ 3.07 (m, 2H); 2.68 (m, 2H); 1.78 (m, 2H); 1.61 (m, 2H), 1.39 (3H, d, JH-C—P=13.6 Hz.); 31P NMR: δ 29 ppm; ESMS (m/z): (M+1)+ found, 134. The mixture was filtered through Celite all solvents were removed under reduced pressure The product was triturated in hot ethanol (50 mL) cooled the solution was diluted with ether (300 mL) The white crystalline solid was filtered washed with ether (2×50 mL), hexane (2×50 mL) dried in vacuo

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

実験手順: A solution of methyl divinyl phosphine oxide (10.73 g, 92.4 mmol) and benzylamine (11.6 mL, 106.3 mmol) in 1:1 THF/water (250 mL) was heated at reflux for 16 hours. The solvents were removed under reduced pressure. The residue was crystallized from CH2Cl2/ether to give 1-benzyl-4-methyl-[1,4]azaphosphinane 4-oxide as a white solid (13.24 g, 64%). 1H NMR (400 MHz, DMSO) δ 7.13-3.37 (5H, m); 3.6 (2H, s); 2.81 (2H, m); 2.59 (2H, m); 1.7-1.9 (4H, m); 1.42 (3H, d, JH-C—P=13.6 Hz). 31P NMR δ 32 ppm. at reflux for 16 hours The solvents were removed under reduced pressure The residue was crystallized from CH2Cl2/ether