benzyl N-(2-hydroxyethyl)-N-methylcarbamate

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:

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:

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

実験手順: To a stirred solution of ethyl 4-hydroxy-3-methoxybenzoate (2.01 g, 10.25 mmol), N-methyl-N-(benzyloxycarbonyl)ethanolamine (2.11 g, 10.08 mmol), PPh3 (3.26 g, 12.43 mmol) in THF was added DIAD (2.65 mL, 13.46 mmol) and the reaction mixture was heated under reflux overnight. The mixture was evaporated, and the residue was subjected to short column chromatography on silica-gel with n-hexane/EtOAc (5:1, v/v) as eluent to give ethyl 3-methoxy-4-[2-methyl-2-(benzyloxycarbonyl)aminoethoxy]benzoate as a crude product. the reaction mixture was heated under reflux overnight The mixture was evaporated

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

実験手順: To a stirred and cooled (0° C.) solution of N-methyl ethanolamine (3.10 g, 41.27 mmol), Et3N (11.80 mL, 84.66 mmol) in DMF—H2O (3:1, v/v, 40 mL) was added dropwise 30% toluene solution of benzyl chloroformate (25.40 g, 49.13 mmol) for over 15 min. The resulting mixture was stirred for 1 day at room temp. The mixture was extracted with EtOAc. The extract was washed with sat. NaHCO3, brine, dried over Na2SO4, and evaporated. The residue was purified by column chromatography on silica-gel with n-hexane:EtOAc (3:1, v/v) then CHCl3 as eluent to give 4.67 g (54%) N-methyl-N-(benzyloxy carbonyl)ethanolamine as a colorless oil. 1H-NMR (CDCl3) d 1.82 (bs, 1 H), 3.00 (s, 3 H), 3.46 (bs, 2 H), 3.77 (bs, 2 H), 5,13 (s, 2 H), 7.29-736 (m, 5 H). The resulting mixture was stirred for 1 day at room temp The mixture was extracted with EtOAc The extract was washed with sat. NaHCO3, brine dried over Na2SO4 evaporated The residue was purified by column chromatography on silica-gel with n-hexane:EtOAc (3:1

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

実験手順: To a stirred solution of ethyl 4-hydoxy-3-methoxybenzoate (2.01 g, 10.25 mmol), N-methyl-N-(benzyloxycarbonyl)ethanolamine (2.11 g, 10.08 mmol), PPh3 (3.26 g, 12.43 mmol) in THF was added DIAD (2.65 mL, 13.46 mmol) and the reaction mixture was heated under reflux overnight. The mixture was evaporated, and the residue was subjected to short column chromatography on silica-gel with n-hexane/EtOAc (5:1, v/v) as eluent to give ethyl 3-methoxy-4-[2-methyl-2-(benzyloxycarbonyl)aminoethoxy]benzoate as a crude product. the reaction mixture was heated under reflux overnight The mixture was evaporated

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

実験手順: To a stirred and cooled (0° C.) solution of N-methyl ethanolamine (3.10 g, 41.27 mmol), Et3 N (11.80 mL, 84.66 mmol) in DMF-H2O (3:1, v/v, 40 mL) was added dropwise 30% toluene solution of benzyl chloroformate (25.40 g, 49.13 mmol) for over 15 min. The resulting mixture was stirred for 1 day at room temp. The mixture was extracted with EtOAc. The extract was washed with sat. NaHCO3, brine, dried over Na2SO4, and evaporated. The residue was purified by column chromatography on silica-gel with n-hexane:EtOAc (3:1, v/v) then CHCl3 as eluent to give 4.67 g (54%) N-methyl-N-(benzyloxy carbonyl)ethanolamine as a colorless oil. 1H-NMR (CDCl3) d 1.82 (bs, 1 H), 3.00 (s, 3 H), 3.46 (bs, 2 H), 3.77 (bs, 2 H), 5.13 (s, 2 H), 7.29–7.36 (m, 5 H). The resulting mixture was stirred for 1 day at room temp The mixture was extracted with EtOAc The extract was washed with sat. NaHCO3, brine dried over Na2SO4 evaporated The residue was purified by column chromatography on silica-gel with n-hexane:EtOAc (3:1

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: DMSO (71 mL, 1 mol) and DIPEA (87.1 mL, 0.5 mol) were added to a stirred solution of the product of step (a) (20.9 g, 0.1 mol) in dichloromethane (200 mL) at −10° C. The reaction mixture was stirred at −10° C. for 15 min and then sulfur trioxide pyridine complex (79.6 g, 0.5 mol) was added and the resulting mixture was stirred for 1 hour. The reaction mixture was quenched with addition of 1M hydrochloric acid (200 mL). The organic layer was separated and washed with saturated aqueous sodium bicarbonate (100 mL), brine (100 mL), dried (potassium carbonate) and solvent removed under reduced pressure to give the title compound (20.7 g, ˜100% yield). sulfur trioxide pyridine complex (79.6 g, 0.5 mol) was added the resulting mixture was stirred for 1 hour The reaction mixture was quenched with addition of 1M hydrochloric acid (200 mL) The organic layer was separated washed with saturated aqueous sodium bicarbonate (100 mL), brine (100 mL) dried (potassium carbonate) and solvent removed under reduced pressure

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

実験手順: Benzyl chloroformate (19 g, 111.1 mmol) in THF (20 mL) was added dropwise over 15 min to a stirred solution of 2-(methylamino)ethanol (10 g, 133.3 mmol) in THF (100 mL) and aqueous sodium carbonate (100 mL) at 0° C. The reaction mixture was stirred at 0° C. for 12 h and then extracted with EtOAc (2×200 mL). The organic layer was washed with aqueous sodium carbonate (200 mL) and dried (potassium carbonate) and solvent was removed under reduced pressure to give the title compound (22.5 g, 97% yield). extracted with EtOAc (2×200 mL) The organic layer was washed with aqueous sodium carbonate (200 mL) dried (potassium carbonate) and solvent was removed under reduced pressure