(2R)-2-[(4-甲氧基苯基)甲氨基]丙-1-醇

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

实验步骤: 2-Chloro-2-methylacetyl chloride (8.4 g, 40.0 mmol) was added to a solution of (2R)-2-(4-methoxybenzylamino)-propan-1-ol (7.79 g, 39.9 mmol) and triethylamine (4.5 g, 44.5 mmol) in tetrahydrofuran (100 ml) and the solution was stirred for one hour. The solution was cooled at 0° C. and 28% sodium methoxide in methanol solution (15.4 g, 79.8 mol) was added. When the reaction was complete (checked by thin layer chromatography), excess reagent was decomposed by the addition of water and pH was adjusted to 5-6 with 3N aqueous hydrochloric acid. The solution was partitioned between water and chloroform. The organic layer was washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; 30-50% ethyl acetate in hexane) to afford (2RS,5R)-4-(4-methoxybenzyl)-5-methyl-2-phenylmorpholin-3-one (12.2 g, 39.1 mmol, 98%) as colorless oil. The solution was partitioned between water and chloroform The organic layer was washed with brine dried over magnesium sulfate concentrated under reduced pressure The residue was purified by silica gel column chromatography (eluent; 30-50% ethyl acetate in hexane)

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

实验步骤: Chloroacetyl chloride (15 g, 133 mmol) was added to a solution of (2R)-2-(4-methoxybenzylamino)-propan-1-ol (26 g, 133 mmol) and triethylamine (15 g, 148 mmol) in tetrahydrofuran (200 ml) and the solution was stirred for one hour. The solution was cooled at 0° C. and sodium hydride (60% dispersion in mineral oil, 5.8 g, 145 mol) was added. When the reaction was complete (checked by thin layer chromatography), excess reagent was decomposed by the addition of water and pH was adjusted to 5-6 with 3N aqueous hydrochloric acid. The solution was partitioned between water and chloroform. The organic layer was washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; 5-10% methanol in chloroform) to afford (5R)-4-(4-methoxybenzyl)-5-methylmorpholin-3-one (19.6 g, 83.3 mmol, 63%) as colorless oil. The solution was partitioned between water and chloroform The organic layer was washed with brine dried over magnesium sulfate concentrated under reduced pressure The residue was purified by silica gel column chromatography (eluent; 5-10% methanol in chloroform)

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

实验步骤: Chloroacetyl chloride (15 g, 133 mmol) was added to a solution of (2R)-2-(4-methoxybenzylamino)-propan-1-ol (26 g, 133 mmol) and triethylamine (15 g, 148 mmol) in tetrahydrofuran (200 ml) and the solution was stirred for one hour. The solution was cooled at 0° C. and sodium hydride (60% dispersion in mineral oil, 5.8 g, 145 mol) was added. When the reaction was complete (checked by thin layer chromatography), excess reagent was decomposed by the addition of water and pH was adjusted to 5-6 with 3N aqueous hydrochloric acid. The solution was partitioned between water and chloroform. The organic layer was washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; 5-10% methanol in chloroform) to afford (5R)-4-(4-methoxybenzyl)-5-methylmorpholin-3-one (19.6 g, 83.3 mmol, 63%) as colorless oil. The solution was partitioned between water and chloroform The organic layer was washed with brine dried over magnesium sulfate concentrated under reduced pressure The residue was purified by silica gel column chromatography (eluent; 5-10% methanol in chloroform)

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

实验步骤: 4-Anisaldehyde (18.1 g, 133 mmol) was added to a solution of D-alaninol (10 g, 133 mmol) in methanol (100 ml) with vigorous stirring and the mixture was stirred for 30 minutes. Sodium borohydride (5.0 g, 132 mmol) was added to the ice-cooled solution and stirred for one hour at room temperature. When the reaction was complete (checked by thin layer chromatography), excess reagent was decomposed by the addition of water. The solution was partitioned between water and chloroform. The organic layer was washed with brine, dried over magnesium sulfate. Removal of the solvent under reduced pressure afforded (2R)-2-(4-Methoxybenzylamino)-propan-1-ol (26 g, 133 mmol, 100%) as white crystals. the mixture was stirred for 30 minutes cooled solution stirred for one hour at room temperature The solution was partitioned between water and chloroform The organic layer was washed with brine dried over magnesium sulfate Removal of the solvent under reduced pressure

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

实验步骤: (R)-(−)-2-Amino-1-propanol (10.36 ml, 133 mmol) was added dropwise to a solution of p-anisaldehyde (5.85 g, 42.9 mmol) in methanol (90 ml), and the solution was cooled in an ice-bath. Acetic acid (2.5 ml) and sodium triacetoxyborohydride (10.0 g, 47.2 mmol) were added and the reaction mixture was allowed to warm to room temperature over an hour. The solution was warmed to 40° C. and stirred for a further 48 hours then concentrated under reduced pressure. The residue was partitioned between saturated sodium bicarbonate solution (50 ml) and dichloromethane (100 ml) and the layers were separated. The aqueous phase was extracted with further dichloromethane (10×50 ml), and the combined organic solutions were dried (MgSO4) and evaporated under reduced pressure. The residue was purified twice by column chromatography on silica gel using an elution gradient of dichloromethane:methanol:0.88 ammonia (97:3:0.3 to 90:10:1) to afford the title compound, 6.0 g. 1H-NMR (CDCl3, 400 MHz) δ: 1.04 (d, 3H), 2.80 (m, 1H), 322 (dd, 1H), 3.58 (dd, 1H), 3.62 (d, 1H), 3.78 (m, 4H), 6.82 (d, 2H), 7.20 (d, 2H). LRMS: m/z (ES+) 196 [MH+]. [α]D=−34.85 (c=0.137, methanol) the solution was cooled in an ice-bath The solution was warmed to 40° C. then concentrated under reduced pressure The residue was partitioned between saturated sodium bicarbonate solution (50 ml) and dichloromethane (100 ml) the layers were separated The aqueous phase was extracted with further dichloromethane (10×50 ml) the combined organic solutions were dried (MgSO4) evaporated under reduced pressure The residue was purified twice by column chromatography on silica gel using an elution gradient of dichloromethane

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

实验步骤: (R)-(−)-2-Amino-1-propanol (10.36 ml, 133 mmol) was added dropwise to a solution of p-anisaldehyde (5.85 g, 42.9 mmol) in methanol (90 ml), and the solution was cooled in an ice-bath. Acetic acid (2.5 ml) and sodium triacetoxyborohydride (10.0 g, 47.2 mmol) were added and the reaction mixture was allowed to warm to room temperature over an hour. The solution was warmed to 40° C. and stirred for a further 48 hours then concentrated under reduced pressure. The residue was partitioned between saturated sodium bicarbonate solution (50 ml) and dichloromethane (100 ml) and the layers were separated. The aqueous phase was extracted with further dichloromethane (10×50 ml), and the combined organic solutions were dried (MgSO4) and evaporated under reduced pressure. The residue was purified twice by column chromatography on silica gel using an elution gradient of dichloromethane:methanol:0.88 ammonia (97:3:0.3 to 90:10:1) to afford the title compound, 6.0 g. 1H-NMR (CDCl3, 400 MHz) δ: 1.04 (d, 3H), 2.80 (m, 1H), 322 (dd, 1H), 3.58 (dd, 1H), 3.62 (d, 1H), 3.78 (m, 4H), 6.82 (d, 2H), 7.20 (d, 2H). LRMS: m/z (ES+) 196 [MH+]. [α]D=−34.85 (c=0.137, methanol) the solution was cooled in an ice-bath The solution was warmed to 40° C. then concentrated under reduced pressure The residue was partitioned between saturated sodium bicarbonate solution (50 ml) and dichloromethane (100 ml) the layers were separated The aqueous phase was extracted with further dichloromethane (10×50 ml) the combined organic solutions were dried (MgSO4) evaporated under reduced pressure The residue was purified twice by column chromatography on silica gel using an elution gradient of dichloromethane

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

实验步骤: (R)-(−)-2-Amino-1-propanol (10.36 ml, 133 mmol) was added dropwise to a solution of p-anisaldehyde (5.85 g, 42.9 mmol) in methanol (90 ml), and the solution was cooled in an ice-bath. Acetic acid (2.5 ml) and sodium triacetoxyborohydride (10.0 g, 47.2 mmol) were added and the reaction mixture was allowed to warm to room temperature over an hour. The solution was warmed to 40° C. and stirred for a further 48 hours then concentrated under reduced pressure. The residue was partitioned between saturated sodium bicarbonate solution (50 ml) and dichloromethane (100 ml) and the layers were separated. The aqueous phase was extracted with further dichloromethane (10×50 ml), and the combined organic solutions were dried (MgSO4) and evaporated under reduced pressure. The residue was purified twice by column chromatography on silica gel using an elution gradient of dichloromethane:methanol:0.88 ammonia (97:3:0.3 to 90:10:1) to afford the title compound, 6.0 g. 1H-NMR (CDCl3, 400 MHz) δ: 1.04 (d, 3H), 2.80 (m, 1H), 322 (dd, 1H), 3.58 (dd, 1H), 3.62 (d, 1H), 3.78 (m, 4H), 6.82 (d, 2H), 7.20 (d, 2H). LRMS: m/z (ES+) 196 [MH+]. [α]D=−34.85 (c=0.137, methanol) the solution was cooled in an ice-bath The solution was warmed to 40° C. then concentrated under reduced pressure The residue was partitioned between saturated sodium bicarbonate solution (50 ml) and dichloromethane (100 ml) the layers were separated The aqueous phase was extracted with further dichloromethane (10×50 ml) the combined organic solutions were dried (MgSO4) evaporated under reduced pressure The residue was purified twice by column chromatography on silica gel using an elution gradient of dichloromethane

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

实验步骤: (R)-(−)-2-Amino-1-propanol (10.36 ml, 133 mmol) was added dropwise to a solution of p-anisaldehyde (5.85 g, 42.9 mmol) in methanol (90 ml), and the solution was cooled in an ice-bath. Acetic acid (2.5 ml) and sodium triacetoxyborohydride (10.0 g, 47.2 mmol) were added and the reaction mixture was allowed to warm to room temperature over an hour. The solution was warmed to 40° C. and stirred for a further 48 hours then concentrated under reduced pressure. The residue was partitioned between saturated sodium bicarbonate solution (50 ml) and dichloromethane (100 ml) and the layers were separated. The aqueous phase was extracted with further dichloromethane (10×50 ml), and the combined organic solutions were dried (MgSO4) and evaporated under reduced pressure. The residue was purified twice by column chromatography on silica gel using an elution gradient of dichloromethane:methanol:0.88 ammonia (97:3:0.3 to 90:10:1) to afford the title compound, 6.0 g. 1H-NMR (CDCl3, 400 MHz) δ: 1.04 (d, 3H), 2.80 (m, 1H), 322 (dd, 1H), 3.58 (dd, 1H), 3.62 (d, 1H), 3.78 (m, 4H), 6.82 (d, 2H), 7.20 (d, 2H). LRMS: m/z (ES+) 196 [MH+]. [α]D=−34.85 (c=0.137, methanol) the solution was cooled in an ice-bath The solution was warmed to 40° C. then concentrated under reduced pressure The residue was partitioned between saturated sodium bicarbonate solution (50 ml) and dichloromethane (100 ml) the layers were separated The aqueous phase was extracted with further dichloromethane (10×50 ml) the combined organic solutions were dried (MgSO4) evaporated under reduced pressure The residue was purified twice by column chromatography on silica gel using an elution gradient of dichloromethane

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

实验步骤: 2-Chloro-2-methylacetyl chloride (8.4 g, 40.0 mmol) was added to a solution of (2R)-2-(4-methoxybenzylamino)-propan-1-ol (7.79 g, 39.9 mmol) and triethylamine (4.5 g, 44.5 mmol) in tetrahydrofuran (100 ml) and the solution was stirred for one hour. The solution was cooled at 0° C. and 28% sodium methoxide in methanol solution (15.4 g, 79.8 mol) was added. When the reaction was complete (checked by thin layer chromatography), excess reagent was decomposed by the addition of water and pH was adjusted to 5-6 with 3N aqueous hydrochloric acid. The solution was partitioned between water and chloroform. The organic layer was washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; 30-50% ethyl acetate in hexane) to afford (2RS,5R)-4-(4-methoxybenzyl)-5-methyl-2-phenylmorpholin-3-one (12.2 g, 39.1 mmol, 98%) as colorless oil. The solution was partitioned between water and chloroform The organic layer was washed with brine dried over magnesium sulfate concentrated under reduced pressure The residue was purified by silica gel column chromatography (eluent; 30-50% ethyl acetate in hexane)

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

实验步骤: Chloroacetyl chloride (15 g, 133 mmol) was added to a solution of (2R)-2-(4-methoxybenzylamino)-propan-1-ol (26 g, 133 mmol) and triethylamine (15 g, 148 mmol) in tetrahydrofuran (200 ml) and the solution was stirred for one hour. The solution was cooled at 0° C. and sodium hydride (60% dispersion in mineral oil, 5.8 g, 145 mol) was added. When the reaction was complete (checked by thin layer chromatography), excess reagent was decomposed by the addition of water and pH was adjusted to 5-6 with 3N aqueous hydrochloric acid. The solution was partitioned between water and chloroform. The organic layer was washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; 5-10% methanol in chloroform) to afford (5R)-4-(4-methoxybenzyl)-5-methylmorpholin-3-one (19.6 g, 83.3 mmol, 63%) as colorless oil. The solution was partitioned between water and chloroform The organic layer was washed with brine dried over magnesium sulfate concentrated under reduced pressure The residue was purified by silica gel column chromatography (eluent; 5-10% methanol in chloroform)

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

实验步骤: 4-Anisaldehyde (18.1 g, 133 mmol) was added to a solution of D-alaninol (10 g, 133 mmol) in methanol (100 ml) with vigorous stirring and the mixture was stirred for 30 minutes. Sodium borohydride (5.0 g, 132 mmol) was added to the ice-cooled solution and stirred for one hour at room temperature. When the reaction was complete (checked by thin layer chromatography), excess reagent was decomposed by the addition of water. The solution was partitioned between water and chloroform. The organic layer was washed with brine, dried over magnesium sulfate. Removal of the solvent under reduced pressure afforded (2R)-2-(4-Methoxybenzylamino)-propan-1-ol (26 g, 133 mmol, 100%) as white crystals. the mixture was stirred for 30 minutes cooled solution stirred for one hour at room temperature The solution was partitioned between water and chloroform The organic layer was washed with brine dried over magnesium sulfate Removal of the solvent under reduced pressure

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

实验步骤: (R)-(−)-2-Amino-1-propanol (10.36 ml, 133 mmol) was added dropwise to a solution of p-anisaldehyde (5.85 g, 42.9 mmol) in methanol (90 ml), and the solution was cooled in an ice-bath. Acetic acid (2.5 ml) and sodium triacetoxyborohydride (10.0 g, 47.2 mmol) were added and the reaction mixture was allowed to warm to room temperature over an hour. The solution was warmed to 40° C. and stirred for a further 48 hours then concentrated under reduced pressure. The residue was partitioned between saturated sodium bicarbonate solution (50 ml) and dichloromethane (100 ml) and the layers were separated. The aqueous phase was extracted with further dichloromethane (10×50 ml), and the combined organic solutions were dried (MgSO4) and evaporated under reduced pressure. The residue was purified twice by column chromatography on silica gel using an elution gradient of dichloromethane:methanol:0.88 ammonia (97:3:0.3 to 90:10:1) to afford the title compound, 6.0 g. 1H-NMR (CDCl3, 400 MHz) δ: 1.04 (d, 3H), 2.80 (m, 1H), 322 (dd, 1H), 3.58 (dd, 1H), 3.62 (d, 1H), 3.78 (m, 4H), 6.82 (d, 2H), 7.20 (d, 2H). LRMS: m/z (ES+) 196 [MH+]. [α]D=−34.85 (c=0.137, methanol) the solution was cooled in an ice-bath The solution was warmed to 40° C. then concentrated under reduced pressure The residue was partitioned between saturated sodium bicarbonate solution (50 ml) and dichloromethane (100 ml) the layers were separated The aqueous phase was extracted with further dichloromethane (10×50 ml) the combined organic solutions were dried (MgSO4) evaporated under reduced pressure The residue was purified twice by column chromatography on silica gel using an elution gradient of dichloromethane