N-苄基丙氨醇

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

实验步骤: To a solution of 2-(oxiran-2-yl)pyridine 1-oxide (6.6 g, 48.48 mmol) in ethanol (150 mL) were added (S)-2-(benzylamino)propan-1-ol (16 g, 96.96 mmol) and potassium carbonate (13.3 g, 96.96 mmol), After 24 h, the mixture was concentrated under reduced pressure and the resulting residue was purified via alumina chromatography (1% methanol in dichloromethane) to afford 2-(2-(benzyl((S)-1-hydroxypropan-2-yl)amino)-1-hydroxyethyl)pyridine 1-oxide as a yellow liquid (7 g, 22%). the mixture was concentrated under reduced pressure the resulting residue was purified via alumina chromatography (1% methanol in dichloromethane)

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

实验步骤: A mixture of (2S)-2-[benzylamino]propan-1-ol (1 equivalent) and epichlorohydrin (1 equivalent) was stirred at room temperature overnight. The mixture was cooled down to 0° C. and cold trifluoromethanesulfonic acid (4 equivalents) was added. The flask was equipped with a reflux condenser and the mixture was stirred at 160° C. overnight. The reaction mixture was cooled to room temperature, diluted with CH2Cl2 and quenched with ice water. The mixture was then made basic (pH=12) with a 30% NaOH solution. The two phases were separated, and the aqueous phase was extracted with CH2Cl2. The organic layer was washed with water, brine, dried over Na2SO4 and concentrated to afford a dark brown oil. The crude product contained an equimolar mixture of (2R,5S)-2-(chloromethyl)-5-methyl-4-benzylmorpholine(cis diastereoisomer) and (2S,5S)-2-(chloromethyl)-5-methyl-4-benzylmorpholine(trans diastereoisomer), which were separated by chromatography on silica gel (ethyl acetate/hexanes 1:20 to 1:8). (2S,5S)-2-(chloromethyl)-5-methyl-4-benzyl morpholine was obtained as the isomer with the lower Rf. GC/MS: 239 (15%, M+), Rt=15.08 minutes; LC/MS (m/z): 240.0 (MH+), Rt 1.56 minutes. The mixture was cooled down to 0° C. The flask was equipped with a reflux condenser the mixture was stirred at 160° C. overnight The reaction mixture was cooled to room temperature quenched with ice water The two phases were separated the aqueous phase was extracted with CH2Cl2 The organic layer was washed with water, brine dried over Na2SO4 concentrated to afford a dark brown oil were separated by chromatography on silica gel (ethyl acetate/hexanes 1:20 to 1:8)

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

实验步骤: Sodium triacetoxyborohydride (36.7 g) was added portion wisely to a mixture of (2S)-2-amino-1-propanol (10.0 g) and benzaldehyde (13.53 ml) in a mixture of dichloromethane (140 ml) and acetic acid (8.38 ml) at 0° C. and the whole was stirred at room temperature overnight. The mixture was washed successively with 2N sodium hydroxide and brine, and dried over sodium sulfate. The solution was evaporated under reduced pressure and the resulting residue was purified by column chromatography on silica gel using a mixed solvent of dichloromethane and methanol (30:1). The fractions containing the objective compound were collected and evaporated under reduced pressure to give (2S)-2-benzylamino-1-propanol (15.96 g). The mixture was washed successively with 2N sodium hydroxide and brine dried over sodium sulfate The solution was evaporated under reduced pressure the resulting residue was purified by column chromatography on silica gel using a mixed solvent of dichloromethane and methanol (30:1) The fractions containing the objective compound were collected evaporated under reduced pressure

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of (2S)-2-[(phenylmethyl)amino]-1-propanol (10.52 g, 63.67 mmol) in THF (65 mL) was added a solution of K2CO3 (26.40 g, 191.0 mmol) in water (65 mL). The vigorously stirred mixture was cooled to 0° C., and chloroacetyl chloride (7.10 mL, 89.14 mmol) was added dropwise over 20 min. The mixture was stirred for 1 h, and then an additional portion of chloroacetyl chloride (0.500 mL, 6.278 mmol) was added dropwise. The mixture was stirred for 1 h, and then the mixture was adjusted to pH>13 with 50% aq. NaOH (ca. 20 mL). The mixture was stirred and warmed to room temperature overnight, and then extracted with DCM (250 mL). The organic phase was washed with 1 N aq. HCl, followed by water. The organic phase was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give (5S)-5-methyl-4-(phenylmethyl)-3-morpholinone (12.74 g, 97%) as a colorless oil. LCMS: (M+H)+: 206.1. The mixture was stirred for 1 h The mixture was stirred warmed to room temperature overnight extracted with DCM (250 mL) The organic phase was washed with 1 N aq. HCl The organic phase was dried over anhydrous Na2SO4 filtered concentrated in vacuo

反应条件: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of (2S)-2-amino-1-propanol (5.01 g, 66.70 mmol) in toluene (130 mL) was added benzaldehyde (7.08 mL, 70.05 mmol). The flask was fitted with a Dean-Stark trap, and the solution was heated at 150° C. for 2 h. The solution was then cooled to room temperature and concentrated in vacuo. To a 0° C. solution of the residue in EtOH (130 mL) was added NaBH4 (6.31 g, 166.8 mmol) and sufficient 4 N HCl in dioxane to adjust the pH to ca. 2. The mixture was stirred overnight and then concentrated in vacuo. The residue was partitioned between 1 N aq. HCl (200 mL) and DCM (100 mL). The aqueous phase was washed with a fresh portion of DCM (100 mL), and then adjusted to pH>13 with 6 N aq. NaOH. The aqueous phase was extracted with DCM (2×150 mL), and the combined organic phase was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to provide (2S)-2-[(phenylmethyl)amino]-1-propanol (10.52 g, 95%) as a colorless oil. LCMS: (M+H)+: 166.1. The flask was fitted with a Dean-Stark trap The solution was then cooled to room temperature concentrated in vacuo concentrated in vacuo The residue was partitioned between 1 N aq. HCl (200 mL) and DCM (100 mL) The aqueous phase was washed with a fresh portion of DCM (100 mL) The aqueous phase was extracted with DCM (2×150 mL) the combined organic phase was dried over anhydrous Na2SO4 filtered concentrated in vacuo

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

实验步骤: To a solution of 2-(oxiran-2-yl)pyridine 1-oxide (6.6 g, 48.48 mmol) in ethanol (150 mL) were added (S)-2-(benzylamino)propan-1-ol (16 g, 96.96 mmol) and potassium carbonate (13.3 g, 96.96 mmol), After 24 h, the mixture was concentrated under reduced pressure and the resulting residue was purified via alumina chromatography (1% methanol in dichloromethane) to afford 2-(2-(benzyl((S)-1-hydroxypropan-2-yl)amino)-1-hydroxyethyl)pyridine 1-oxide as a yellow liquid (7 g, 22%). the mixture was concentrated under reduced pressure the resulting residue was purified via alumina chromatography (1% methanol in dichloromethane)