(3R)-4-benzyl-3-methylmorpholine

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

実験手順: A solution of (R)-4-benzyl-5-methylmorpholine-3-one (3.0 g, 14.22 mmol) in THF (10 mL) was added dropwise at 0° C. to a solution of lithium aluminum hydride (1.0 M solution in THF, 28.5 mL, 28.5 mmol) in THF (10 mL). The ice bath was removed and the reaction mixture was heated at reflux for 18 h. The reaction was cooled in an ice-bath and excess hydride reagent was quenched by careful, dropwise addition of H2O (5 mL), 15% sodium hydroxide (5 mL) and H2O (15 mL). The resulting mixture was stirred at room temperature for 1 h and the reaction mixture was filtered through a pad of Celite and the pad rinsed with EtOAc (100 mL). The filtrate was washed with saturated brine solution, dried (Na2SO4), filtered and concentrated under reduced pressure to provide (R)-4-benzyl-3-methylmorpholine (2.66 g, 95%) as a red oil. 1H NMR and MS consistent. The ice bath was removed the reaction mixture was heated at reflux for 18 h The reaction was cooled in an ice-bath excess hydride reagent was quenched by careful, dropwise addition of H2O (5 mL), 15% sodium hydroxide (5 mL) and H2O (15 mL) the reaction mixture was filtered through a pad of Celite the pad rinsed with EtOAc (100 mL) The filtrate was washed with saturated brine solution dried (Na2SO4) filtered concentrated under reduced pressure

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

実験手順: A solution of (R)-4-benzyl-5-methylmorpholine-3-one (3.0 g, 14.22 mmol) in THF (10 mL) was added dropwise at 0° C. to a solution of lithium aluminum hydride (1.0 M solution in THF, 28.5 mL, 28.5 mmol) in THF (10 mL). The ice bath was removed and the reaction mixture was heated at reflux for 18 h. The reaction was cooled in an ice-bath and excess hydride reagent was quenched by careful, dropwise addition of H2O (5 mL), 15% sodium hydroxide (5 mL) and H2O (15 mL). The resulting mixture was stirred at room temperature for 1 h and the reaction mixture was filtered through a pad of Celite and the pad rinsed with EtOAc (100 mL). The filtrate was washed with saturated brine solution, dried (Na2SO4), filtered and concentrated under reduced pressure to provide (R)-4-benzyl-3-methylmorpholine (2.66 g, 95%) as a red oil. 1H NMR and MS consistent. The ice bath was removed the reaction mixture was heated at reflux for 18 h The reaction was cooled in an ice-bath excess hydride reagent was quenched by careful, dropwise addition of H2O (5 mL), 15% sodium hydroxide (5 mL) and H2O (15 mL) the reaction mixture was filtered through a pad of Celite the pad rinsed with EtOAc (100 mL) The filtrate was washed with saturated brine solution dried (Na2SO4) filtered concentrated under reduced pressure

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

実験手順: A solution of (R)-4-benzyl-5-methylmorpholine-3-one (3.0 g, 14.22 mmol) in THF (10 mL) was added dropwise at 0° C. to a solution of lithium aluminum hydride (1.0 M solution in THF, 28.5 mL, 28.5 mmol) in THF (10 mL). The ice bath was removed and the reaction mixture was heated at reflux for 18 h. The reaction was cooled in an ice-bath and excess hydride reagent was quenched by careful, dropwise addition of H2O (5 mL), 15% sodium hydroxide (5 mL) and H2O (15 mL). The resulting mixture was stirred at room temperature for 1 h and the reaction mixture was filtered through a pad of Celite and the pad rinsed with EtOAc (100 mL). The filtrate was washed with saturated brine solution, dried (Na2SO4), filtered and concentrated under reduced pressure to provide (R)-4-benzyl-3-methylmorpholine (2.66 g, 95%) as a red oil. 1H NMR and MS consistent. The ice bath was removed the reaction mixture was heated at reflux for 18 h The reaction was cooled in an ice-bath excess hydride reagent was quenched by careful, dropwise addition of H2O (5 mL), 15% sodium hydroxide (5 mL) and H2O (15 mL) the reaction mixture was filtered through a pad of Celite the pad rinsed with EtOAc (100 mL) The filtrate was washed with saturated brine solution dried (Na2SO4) filtered concentrated under reduced pressure

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of (5R)-5-methyl-4-(phenylmethyl)-3-morpholinone (11.7 g, 57 mmol) in toluene (140 mL) at 0° C. was added sodium bis(2-methoxyethoxy)aluminumhydride (Red-Al) (35 mL, 3 mL/g of morpholinone) slowly via addition funnel, and the reaction mixture was stirred overnight at 60° C. The reaction was cooled down to 0° C. and quenched by dropwise addition of 1N aqueous NaOH (15 mL). The resulting mixture was partitioned between Et2O (100 mL) and of 1N aqueous NaOH (100 mL). The organic layer was separated, and the aqueous layer was further extracted with Et2O (50 mL). The combined organic layers were dried (Na2SO4), filtered and concentrated. The resulting residue was azeotroped with CH3OH (50 mL) to afford the title compound (10.69 g) as a colorless oil. LC-MS (ES) m/z=192 [M+H]+ slowly via addition funnel The reaction was cooled down to 0° C. quenched by dropwise addition of 1N aqueous NaOH (15 mL) The resulting mixture was partitioned between Et2O (100 mL) and of 1N aqueous NaOH (100 mL) The organic layer was separated the aqueous layer was further extracted with Et2O (50 mL) The combined organic layers were dried (Na2SO4) filtered concentrated The resulting residue was azeotroped with CH3OH (50 mL)

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

実験手順: (R)-4-Benzyl-5-methylmorpholin-3-one (5.05 g, 24.6 mmol) was dissolved in THF (12.3 mL) before lithium aluminum hydride (1.87 g, 49.2 mmol) was added and the mixture stirred at RT for 1 h. The reaction mixture was quenched with ethyl acetate before a few drops of ammonium chloride was added. The colorless oil was filtered, washed with dichloromethane, concentrated, and purified by flash chromatography to give the title compound. MS (ES+): 192(M+H)+. was added The reaction mixture was quenched with ethyl acetate before a few drops of ammonium chloride was added The colorless oil was filtered washed with dichloromethane concentrated purified by flash chromatography

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

実験手順: (R)-4-Benzyl-5-methylmorpholin-3-one (5.05 g, 24.6 mmol) was dissolved in THF (12.3 mL) before lithium aluminum hydride (1.87 g, 49.2 mmol) was added and the mixture stirred at RT for 1 h. The reaction mixture was quenched with ethyl acetate before a few drops of ammonium chloride was added. The colorless oil was filtered, washed with dichloromethane, concentrated, and purified by flash chromatography to give the title compound. MS (ES+): 192(M+H)+. was added The reaction mixture was quenched with ethyl acetate before a few drops of ammonium chloride was added The colorless oil was filtered washed with dichloromethane concentrated purified by flash chromatography

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

実験手順: A solution of (R)-4-benzyl-5-methylmorpholine-3-one (3.0 g, 14.22 mmol) in THF (10 mL) was added dropwise at 0° C. to a solution of lithium aluminum hydride (1.0 M solution in THF, 28.5 mL, 28.5 mmol) in THF (10 mL). The ice bath was removed and the reaction mixture was heated at reflux for 18 h. The reaction was cooled in an ice-bath and excess hydride reagent was quenched by careful, dropwise addition of H2O (5 mL), 15% sodium hydroxide (5 mL) and H2O (15 mL). The resulting mixture was stirred at room temperature for 1 h and the reaction mixture was filtered through a pad of Celite and the pad rinsed with EtOAc (100 mL). The filtrate was washed with saturated brine solution, dried (Na2SO4), filtered and concentrated under reduced pressure to provide (R)-4-benzyl-3-methylmorpholine (2.66 g, 95%) as a red oil. 1H NMR and MS consistent. The ice bath was removed the reaction mixture was heated at reflux for 18 h The reaction was cooled in an ice-bath excess hydride reagent was quenched by careful, dropwise addition of H2O (5 mL), 15% sodium hydroxide (5 mL) and H2O (15 mL) the reaction mixture was filtered through a pad of Celite the pad rinsed with EtOAc (100 mL) The filtrate was washed with saturated brine solution dried (Na2SO4) filtered concentrated under reduced pressure