反应详情

温度

25 °C

To a mixture of N-benzylethanolamine (40.9 g, 0.270 mol), 2-propanol (25 ml) and water (25 ml) was added dropwise at 15 to 25° C. (S)-epichlorohydrin (25.0 g, 0.270 mol, 99% ee). After reaction at 15 to 25° C. for 7 hr, aqueous 24% NaOH solution (NET 14.05 g, 0.351 mol) was added at 5 to 10° C. After reaction at 25° C. for 20 hr, the reaction mixture was concentrated under reduced pressure to evaporate 2-propanol. To the residue was added toluene (75 ml) and, after partitioning, the organic layer was concentrated under reduced pressure. To the obtained residue (53.9 g) were added methanol (161.8 ml) and palladium carbon (18.9 g when dry), and the mixture was reacted under a hydrogen stream at 40° C. for 30 hr. Palladium carbon was filtered off, and the filtrate was concentrated under reduced pressure and the residue was distilled (0.5 mmHg, 115 to 135° C.) to give a mixture of 2-hydroxymethylmorpholine and 1,4-oxazepane compound (21.6 g, 2-hydroxymethylmorpholine: 1,4-oxazepane compound=79.0:21.0). To this mixture was added methanol (22 ml), and trifluoroacetic acid (22.1 g, 0.194 mol) was added dropwise at 0 to 25° C. After stirring at 25° C. for 1 hr, the mixture was concentrated under reduced pressure. To the residue was added ethyl acetate (108 ml) at 40° C., and the mixture was cooled to 20° C. Seed crystal was added and, 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 (22 ml) and dried (1 mmHg, 40° C.) to give (R)-2-hydroxymethylmorpholine trifluoroacetate (26.49 g) (yield from (S)-epichlorohydrin 42.4%). The obtained (R)-2-hydroxymethylmorpholine trifluoroacetate was analyzed by HPLC to find an optical purity of 99% ee.

1. customAfter reaction at 15 to 25° C. for 7 hr
2. customAfter reaction at 25° C. for 20 hr
3. concentrationthe reaction mixture was concentrated under reduced pressure
4. customto evaporate 2-propanol
5. additionTo the residue was added toluene (75 ml)
6. customafter partitioning
7. concentrationthe organic layer was concentrated under reduced pressure
8. additionTo the obtained residue (53.9 g) were added methanol (161.8 ml) and palladium carbon (18.9 g when dry)
9. customthe mixture was reacted under a hydrogen stream at 40° C. for 30 hr
10. filtrationPalladium carbon was filtered off
11. concentrationthe filtrate was concentrated under reduced pressure
12. distillationthe residue was distilled (0.5 mmHg, 115 to 135° C.)
13. customto give
14. additionwas added dropwise at 0 to 25° C
15. concentrationthe mixture was concentrated under reduced pressure
16. additionTo the residue was added ethyl acetate (108 ml) at 40° C.
17. temperaturethe mixture was cooled to 20° C
18. additionSeed crystal was added
19. customafter crystallization
20. temperaturethe mixture was cooled to 0° C.
21. stirringstirred for 1 hr
22. filtrationThe crystals were collected by filtration
23. washwashed
24. customdried (1 mmHg, 40° C.)