反応 #328481

反応方程式

trifluoroacetic acid

N-benzylethanolamine

(S)-epichlorohydrin

N-benzyl-2-hydroxymethylmorpholine

N-benzyl-1,4-oxazepane

NaOH

→

(R)-2-hydroxymethylmorpholine trifluoroacetate

溶媒

methanol

water

2-propanol

反応条件

後処理

1. 1
   その他After reaction at 15 to 25° C. for 7 hr
2. 2
   その他After reaction at 25° C. for 20 hr
3. 3
   濃縮the reaction mixture was concentrated under reduced pressure
4. 4
   その他to evaporate 2-propanol
5. 5
   workup.ADDITIONTo the residue was added toluene (150 ml)
6. 6
   その他after partitioning
7. 7
   濃縮the organic layer was concentrated under reduced pressure
8. 8
   workup.DISTILLATIONThe residue was distilled (0.5 mmHg, 150 to 180° C.)
9. 9
   その他to give
10. 10
    その他the mixture was reacted under hydrogen stream at 25° C. for 15 hr
11. 11
    ろ過Palladium carbon was filtered off
12. 12
    濃縮the filtrate was concentrated under reduced pressure
13. 13
    workup.DISTILLATIONThe residue was subjected twice to azeotropic distillation
14. 14
    workup.DISTILLATIONTo the residue after azeotropic distillation with dehydrating
15. 15
    workup.ADDITIONwas added ethyl acetate (150 ml) at 40° C.
16. 16
    その他After crystallization
17. 17
    ろ過The crystal was collected by filtration
18. 18
    洗浄washed twice with ethyl acetate (76 ml)
19. 19
    その他dried (1 mmHg, 40° C.)

実験手順

To a mixture of N-benzylethanolamine (81.7 g, 0.540 mol), 2-propanol (50 ml) and water (50 ml) was added dropwise at 15 to 25° C. (S)-epichlorohydrin (50.0 g, 0.540 mol, 99% ee). After reaction at 15 to 25° C. for 7 hr, aqueous 24% NaOH solution (NET 28.1 g, 0.703 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 (150 ml) and, after partitioning, the organic layer was concentrated under reduced pressure. The residue was distilled (0.5 mmHg, 150 to 180° C.) to give a mixture of N-benzyl-2-hydroxymethylmorpholine and N-benzyl-1,4-oxazepane compound (about 70 g, N-benzyl-2-hydroxymethylmorpholine:N-benzyl-1,4-oxazepane compound=76:24). To this mixture (50.0 g) were added methanol (150 ml), trifluoroacetic acid (27.5 g, 0.241 mol) and palladium carbon (10.0 g when dry), and the mixture was reacted under hydrogen stream at 25° C. for 15 hr. Palladium carbon was filtered off, and the filtrate was concentrated under reduced pressure. The residue was subjected twice to azeotropic distillation with dehydrating with 2-propanol (50 ml). To the residue after azeotropic distillation with dehydrating was added ethyl acetate (150 ml) at 40° C., and the mixture was cooled to 10° C. After crystallization, the mixture was further stirred for 1 hr. The crystal was collected by filtration, washed twice with ethyl acetate (76 ml) and dried (1 mmHg, 40° C.) to give (R)-2-hydroxymethylmorpholine trifluoroacetate as crystals (about 20 to 25 g). The obtained crystals were used as a seed crystal in the following Examples.

出典