1,4-oxazepane

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:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of 2-hydroxymethylmorpholine and 1,4-oxazepane compound (20.0 g, 2-hydroxymethylmorpholine:1,4-oxazepane compound=75.8:24.2) synthesized in Example 5 were added methanol (100 ml) and terephthalic acid (12.5 g, 0.075 mol) and the mixture was stirred for 30 min. Methanol was evaporated under reduced pressure. To the residue was added 2-propanol (50 ml) and the mixture was subjected twice to azeotropic distillation with dehydrating. To the residue after azeotropic distillation with dehydrating was added ethyl acetate (100 ml) at 40° C., and the mixture was cooled to 10° C. After crystallization, the mixture was cooled to 0° C. and stirred for 1 hr. The crystals were collected by filtration, washed withed twice with ethyl acetate (25 ml) and dried (1 mmHg, 40° C.) to give (R)-2-hydroxymethylmorpholine terephthalate (10.1 g) (2-hydroxymethylmorpholine:terephthalic acid=2:1, yield from (S)-epichlorohydrin: 33.5%). The obtained (R)-2-hydroxymethylmorpholine terephthalate was analyzed by HPLC to find an optical purity of 99% ee. synthesized in Example 5 Methanol was evaporated under reduced pressure To the residue was added 2-propanol (50 ml) the mixture was subjected twice to azeotropic distillation with dehydrating To the residue after azeotropic distillation with dehydrating was added ethyl acetate (100 ml) at 40° C. After crystallization the mixture was cooled to 0° C. stirred for 1 hr The crystals were collected by filtration washed dried (1 mmHg, 40° C.)

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

実験手順: To a mixture of 2-hydroxymethylmorpholine and 1,4-oxazepane compound (20.0 g, 2-hydroxymethylmorpholine:1,4-oxazepane compound=75.8:24.2) synthesized in Example 5 were added methanol (100 ml) and terephthalic acid (12.5 g, 0.075 mol) and the mixture was stirred for 30 min. Methanol was evaporated under reduced pressure. To the residue was added 2-propanol (50 ml) and the mixture was subjected twice to azeotropic distillation with dehydrating. To the residue after azeotropic distillation with dehydrating was added ethyl acetate (100 ml) at 40° C., and the mixture was cooled to 10° C. After crystallization, the mixture was cooled to 0° C. and stirred for 1 hr. The crystals were collected by filtration, washed withed twice with ethyl acetate (25 ml) and dried (1 mmHg, 40° C.) to give (R)-2-hydroxymethylmorpholine terephthalate (10.1 g) (2-hydroxymethylmorpholine:terephthalic acid=2:1, yield from (S)-epichlorohydrin: 33.5%). The obtained (R)-2-hydroxymethylmorpholine terephthalate was analyzed by HPLC to find an optical purity of 99% ee. synthesized in Example 5 Methanol was evaporated under reduced pressure To the residue was added 2-propanol (50 ml) the mixture was subjected twice to azeotropic distillation with dehydrating To the residue after azeotropic distillation with dehydrating was added ethyl acetate (100 ml) at 40° C. After crystallization the mixture was cooled to 0° C. stirred for 1 hr The crystals were collected by filtration washed dried (1 mmHg, 40° C.)

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

実験手順: To a mixture of 2-hydroxymethylmorpholine and 1,4-oxazepane compound (20.0 g, 2-hydroxymethylmorpholine:1,4-oxazepane compound=75.8:24.2) synthesized in Example 5 were added methanol (100 ml) and maleic acid (17.5 g, 0.151 mol) and the mixture was stirred for 30 min. Methanol was evaporated under reduced pressure. To the residue was added 2-propanol (50 ml) and the mixture was subjected twice to azeotropic distillation with dehydrating. To the residue after azeotropic distillation with dehydrating was added ethyl acetate (100 ml) at 40° C., and the mixture was cooled to 10° C. After crystallization, the mixture was cooled to 0° C. and stirred for 1 hr. The crystals were collected by filtration, washed withed twice with ethyl acetate (25 ml) and dried (1 mmHg, 40° C.) to give (R)-2-hydroxymethylmorpholine maleate (13.8 g) (2-hydroxymethylmorpholine:maleic acid=1:1, yield from (S)-epichlorohydrin: 39.2%). The obtained (R)-2-hydroxymethylmorpholine maleate was analyzed by HPLC to find an optical purity of 99% ee. synthesized in Example 5 Methanol was evaporated under reduced pressure To the residue was added 2-propanol (50 ml) the mixture was subjected twice to azeotropic distillation with dehydrating To the residue after azeotropic distillation with dehydrating was added ethyl acetate (100 ml) at 40° C. After crystallization the mixture was cooled to 0° C. stirred for 1 hr The crystals were collected by filtration washed dried (1 mmHg, 40° C.)

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

実験手順: To a mixture of 2-hydroxymethylmorpholine and 1,4-oxazepane compound (20.0 g, 2-hydroxymethylmorpholine:1,4-oxazepane compound=75.8:24.2) synthesized in Example 5 were added methanol (100 ml) and maleic acid (17.5 g, 0.151 mol) and the mixture was stirred for 30 min. Methanol was evaporated under reduced pressure. To the residue was added 2-propanol (50 ml) and the mixture was subjected twice to azeotropic distillation with dehydrating. To the residue after azeotropic distillation with dehydrating was added ethyl acetate (100 ml) at 40° C., and the mixture was cooled to 10° C. After crystallization, the mixture was cooled to 0° C. and stirred for 1 hr. The crystals were collected by filtration, washed withed twice with ethyl acetate (25 ml) and dried (1 mmHg, 40° C.) to give (R)-2-hydroxymethylmorpholine maleate (13.8 g) (2-hydroxymethylmorpholine:maleic acid=1:1, yield from (S)-epichlorohydrin: 39.2%). The obtained (R)-2-hydroxymethylmorpholine maleate was analyzed by HPLC to find an optical purity of 99% ee. synthesized in Example 5 Methanol was evaporated under reduced pressure To the residue was added 2-propanol (50 ml) the mixture was subjected twice to azeotropic distillation with dehydrating To the residue after azeotropic distillation with dehydrating was added ethyl acetate (100 ml) at 40° C. After crystallization the mixture was cooled to 0° C. stirred for 1 hr The crystals were collected by filtration washed dried (1 mmHg, 40° C.)

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

実験手順: To a mixture of 2-hydroxymethylmorpholine and 1,4-oxazepane compound (20.0 g, 2-hydroxymethylmorpholine:1,4-oxazepane compound=75.8:24.2) synthesized in Example 5 were added methanol (100 ml) and fumaric acid (17.5 g, 0.151 mol) and the mixture was stirred for 30 min. Methanol was evaporated under reduced pressure. To the residue was added 2-propanol (50 ml) and the mixture was subjected twice to azeotropic distillation with dehydrating. To the residue after azeotropic distillation with dehydrating was added ethyl acetate (100 ml) at 40° C., and the mixture was cooled to 10° C. After crystallization, the mixture was cooled to 0° C. and stirred for 1 hr. The crystals were collected by filtration, washed withed twice with ethyl acetate (25 ml) and dried (1 mmHg, 40° C.) to give (R)-2-hydroxymethylmorpholine fumarate (14.8 g) (2-hydroxymethylmorpholine:fumaric acid=1:1, yield from (S)-epichlorohydrin: 42.2%). The obtained (R)-2-hydroxymethylmorpholine fumarate was analyzed by HPLC to find an optical purity of 99% ee. synthesized in Example 5 Methanol was evaporated under reduced pressure To the residue was added 2-propanol (50 ml) the mixture was subjected twice to azeotropic distillation with dehydrating To the residue after azeotropic distillation with dehydrating was added ethyl acetate (100 ml) at 40° C. After crystallization the mixture was cooled to 0° C. stirred for 1 hr The crystals were collected by filtration washed dried (1 mmHg, 40° C.)

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

実験手順: To a mixture of 2-hydroxymethylmorpholine and 1,4-oxazepane compound (20.0 g, 2-hydroxymethylmorpholine:1,4-oxazepane compound=75.8:24.2) synthesized in Example 5 were added methanol (100 ml) and fumaric acid (17.5 g, 0.151 mol) and the mixture was stirred for 30 min. Methanol was evaporated under reduced pressure. To the residue was added 2-propanol (50 ml) and the mixture was subjected twice to azeotropic distillation with dehydrating. To the residue after azeotropic distillation with dehydrating was added ethyl acetate (100 ml) at 40° C., and the mixture was cooled to 10° C. After crystallization, the mixture was cooled to 0° C. and stirred for 1 hr. The crystals were collected by filtration, washed withed twice with ethyl acetate (25 ml) and dried (1 mmHg, 40° C.) to give (R)-2-hydroxymethylmorpholine fumarate (14.8 g) (2-hydroxymethylmorpholine:fumaric acid=1:1, yield from (S)-epichlorohydrin: 42.2%). The obtained (R)-2-hydroxymethylmorpholine fumarate was analyzed by HPLC to find an optical purity of 99% ee. synthesized in Example 5 Methanol was evaporated under reduced pressure To the residue was added 2-propanol (50 ml) the mixture was subjected twice to azeotropic distillation with dehydrating To the residue after azeotropic distillation with dehydrating was added ethyl acetate (100 ml) at 40° C. After crystallization the mixture was cooled to 0° C. stirred for 1 hr The crystals were collected by filtration washed dried (1 mmHg, 40° C.)

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

実験手順: To a mixture of 2-hydroxymethylmorpholine and 1,4-oxazepane compound (20.0 g, 2-hydroxymethylmorpholine:1,4-oxazepane compound=75.8:24.2) synthesized in Example 5 were added methanol (100 ml) and oxalic acid (13.6 g, 0.151 mol) and the mixture was stirred for 30 min. Methanol was evaporated under reduced pressure. To the residue was added 2-propanol (50 ml) and the mixture was subjected twice to azeotropic distillation with dehydrating. To the residue after azeotropic distillation with dehydrating was added ethyl acetate (100 ml) at 40° C., and the mixture was cooled to 10° C. After crystallization, the mixture was cooled to 0° C. and stirred for 1 hr. The crystals were collected by filtration, washed withed twice with ethyl acetate (25 ml) and dried (1 mmHg, 40° C.) to give (R)-2-hydroxymethylmorpholine oxalate (12.6 g) (2-hydroxymethylmorpholine:oxalic acid=1:1, yield from (S)-epichlorohydrin 40.5%). The obtained (R)-2-hydroxymethylmorpholine oxalate was analyzed by HPLC to find an optical purity of 99% ee. synthesized in Example 5 Methanol was evaporated under reduced pressure To the residue was added 2-propanol (50 ml) the mixture was subjected twice to azeotropic distillation with dehydrating To the residue after azeotropic distillation with dehydrating was added ethyl acetate (100 ml) at 40° C. After crystallization the mixture was cooled to 0° C. stirred for 1 hr The crystals were collected by filtration washed dried (1 mmHg, 40° C.)

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

実験手順: To a mixture of 2-hydroxymethylmorpholine and 1,4-oxazepane compound (20.0 g, 2-hydroxymethylmorpholine:1,4-oxazepane compound=75.8:24.2) synthesized in Example 5 were added methanol (100 ml) and oxalic acid (13.6 g, 0.151 mol) and the mixture was stirred for 30 min. Methanol was evaporated under reduced pressure. To the residue was added 2-propanol (50 ml) and the mixture was subjected twice to azeotropic distillation with dehydrating. To the residue after azeotropic distillation with dehydrating was added ethyl acetate (100 ml) at 40° C., and the mixture was cooled to 10° C. After crystallization, the mixture was cooled to 0° C. and stirred for 1 hr. The crystals were collected by filtration, washed withed twice with ethyl acetate (25 ml) and dried (1 mmHg, 40° C.) to give (R)-2-hydroxymethylmorpholine oxalate (12.6 g) (2-hydroxymethylmorpholine:oxalic acid=1:1, yield from (S)-epichlorohydrin 40.5%). The obtained (R)-2-hydroxymethylmorpholine oxalate was analyzed by HPLC to find an optical purity of 99% ee. synthesized in Example 5 Methanol was evaporated under reduced pressure To the residue was added 2-propanol (50 ml) the mixture was subjected twice to azeotropic distillation with dehydrating To the residue after azeotropic distillation with dehydrating was added ethyl acetate (100 ml) at 40° C. After crystallization the mixture was cooled to 0° C. stirred for 1 hr The crystals were collected by filtration washed dried (1 mmHg, 40° C.)