Reaktion #59676

Reaktionsgleichung

hydrochloric acid

Ammonium hydroxide

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

acetate

→

off-white solid

Ausbeute 95.0%

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

Ausbeute 95.0%

Lösungsmittel

Methanol

toluene

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe organic layer was collected
2. 2
   Waschenwashed with deionized water (26 ml)
3. 3
   Einengenconcentrated to ca. 30 ml
4. 4
   Sonstigeto remove traces of water azetropically
5. 5
   workup.ADDITION(R)-3-Chlorostyrene oxide (5.17 g) was added
6. 6
   TemperaturThe 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
    Sonstigethe homogeneous solution obtained
11. 11
    Temperaturwas heated
12. 12
    Temperaturat reflux (ca. 4 h) until the hydrolysis
13. 13
    TemperaturThe mixture was cooled to <50° C
14. 14
    workup.ADDITIONThe reaction mixture from above was added over 20 min
15. 15
    Temperaturthe resultant slurry was cooled to <20° C.
16. 16
    workup.WAITaged for a further 30 min
17. 17
    FiltrationThe product was collected by filtration
18. 18
    Waschenwashed with deionized water (2×26 ml)
19. 19
    Sonstigedried in vacuo at 50° C.

Vorschrift

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.

Quelle