تفاعل #328484

معادلة التفاعل

trifluoroacetic acid

N-benzylethanolamine

(S)-epichlorohydrin

N-benzyl-2-hydroxymethylmorpholine

N-benzyl-1,4-oxazepane

NaOH

→

(R)-2-hydroxymethylmorpholine trifluoroacetate

المردود 41.1%

المذيبات

water

2-propanol

methanol

ظروف التفاعل

المعالجة

1. 1
   أخرىAfter reaction at 10 to 25° C. for 7 hr
2. 2
   أخرىAfter reaction at 25° C. for 20 hr
3. 3
   تركيزthe reaction mixture was concentrated under reduced pressure
4. 4
   أخرىto evaporate 2-propanol
5. 5
   workup.ADDITIONTo the residue was added toluene (150 ml)
6. 6
   أخرىafter partitioning
7. 7
   تركيزthe organic layer was concentrated under reduced pressure
8. 8
   أخرىto give
9. 9
   أخرىthe mixture was reacted under a hydrogen stream at 25° C. for 15 hr
10. 10
    ترشيحPalladium carbon was filtered off
11. 11
    أخرىmethanol was evaporated under reduced pressure
12. 12
    workup.DISTILLATIONThe residue was subjected twice to azeotropic distillation
13. 13
    workup.DISTILLATIONTo the residue after azeotropic distillation with dehydrating
14. 14
    workup.ADDITIONwas added ethyl acetate (450 ml) at 40° C.
15. 15
    workup.ADDITIONSeed crystal was added
16. 16
    أخرىafter crystallization
17. 17
    درجة الحرارةthe mixture was cooled to 0° C.
18. 18
    ترشيحThe crystals were collected by filtration
19. 19
    غسيلwashed
20. 20
    أخرىdried (1 mmHg, 40° C.)

الإجراء التجريبي

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 10 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 to give a mixture of N-benzyl-2-hydroxymethylmorpholine and N-benzyl-1,4-oxazepane (125.3 g, N-benzyl-2-hydroxymethylmorpholine:N-benzyl-1,4-oxazepane compound=74.4:25.6). To this mixture were added methanol (200 ml) and palladium carbon (11.0 g when dry), and the mixture was reacted under a hydrogen stream at 25° C. for 15 hr. Palladium carbon was filtered off, trifluoroacetic acid (61.8 g, 0.540 mol) was added to the filtrate at 5 to 10° C., and methanol was evaporated under reduced pressure. The residue was subjected twice to azeotropic distillation with dehydrating with 2-propanol (100 ml). To the residue after azeotropic distillation with dehydrating was added ethyl acetate (450 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 (100 ml) and dried (1 mmHg, 40° C.) to give (R)-2-hydroxymethylmorpholine trifluoroacetate (51.3 g) (yield from (S)-epichlorohydrin 41.1%). The obtained (R)-2-hydroxymethylmorpholine trifluoroacetate was analyzed by HPLC to find an optical purity of 99% ee.

المصدر