반응 #59676

반응 방정식

hydrochloric acid

Ammonium hydroxide

ethyl 2-[3-(2-methyl-4,5-dihydro-1H-imidazol-1-yl)phenyl]-3-furoate

acetate

→

off-white solid

수율 95.0%

2-{3-[(2-{[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]-amino}ethyl)amino]phenyl}-3-furoic acid

수율 95.0%

용매

Methanol

toluene

water

반응 조건

후처리

1. 1
   기타the organic layer was collected
2. 2
   세척washed with deionized water (26 ml)
3. 3
   농축concentrated to ca. 30 ml
4. 4
   기타to remove traces of water azetropically
5. 5
   workup.ADDITION(R)-3-Chlorostyrene oxide (5.17 g) was added
6. 6
   온도The mixture was cooled to ca. 50° C
7. 7
   workup.ADDITION1M Sodium hydroxide aqueous solution (77.8 ml) and methanol (39 ml) were added
8. 8
   workup.DISTILLATIONthe apparatus was configured for distillation
9. 9
   workup.WAITAfter ca. 1 h
10. 10
    기타the homogeneous solution obtained
11. 11
    온도was heated
12. 12
    온도at reflux (ca. 4 h) until the hydrolysis
13. 13
    온도The mixture was cooled to <50° C
14. 14
    workup.ADDITIONThe reaction mixture from above was added over 20 min
15. 15
    온도the resultant slurry was cooled to <20° C.
16. 16
    workup.WAITaged for a further 30 min
17. 17
    여과The product was collected by filtration
18. 18
    세척washed with deionized water (2×26 ml)
19. 19
    기타dried in vacuo at 50° C.

실험 절차

Ammonium hydroxide (28%, 13 ml) was added over 10 min. to a mixture of ethyl 2-[3-(2-methyl-4,5-dihydro-1H-imidazol-1-yl)phenyl]-3-furoate (13.0 g), deionized water (104 ml), and toluene (104 ml). After 30 min stirring, the organic layer was collected, washed with deionized water (26 ml), and concentrated to ca. 30 ml to remove traces of water azetropically. (R)-3-Chlorostyrene oxide (5.17 g) was added, and the resultant was heated under nitrogen at 110° C. for at least 14 h. The mixture was cooled to ca. 50° C. 1M Sodium hydroxide aqueous solution (77.8 ml) and methanol (39 ml) were added, and the apparatus was configured for distillation. After ca. 1 h, the homogeneous solution obtained was heated at reflux (ca. 4 h) until the hydrolysis was complete (HPLC acetate <2% @ 220 nm, a/a). The mixture was cooled to <50° C. Methanol (26 ml) and 1M hydrochloric acid (78 ml) were heated to ca. 50° C. The reaction mixture from above was added over 20 min, and the resultant slurry was cooled to <20° C. and aged for a further 30 min. The product was collected by filtration, washed with deionized water (2×26 ml), and dried in vacuo at 50° C. to yield 12.7 g (95%) of off-white solid.

출처