Reacción #66277

Ecuación de reacción

(E)-ethyl 3-(4-bromo-2-nitrophenyl)-2-(cyanomethyl)acrylate

NaHCO3

EtOAc

→

(1E,4E)-ethyl 2-amino-8-bromo-3H-benzo[b]azepine-4-carboxylate

Rendimiento 91.0%

Disolventes

AcOH

water

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrothe internal temperature below 100° C
2. 2
   Temperaturathe reaction mixture was heated for additional 2.5 h at 80-85° C. until the starting material
3. 3
   TemperaturaThe reaction mixture was cooled to room temperature
4. 4
   Filtraciónfiltered through a GF/F
5. 5
   Filtraciónfilter
6. 6
   Lavadorinsing with AcOH
7. 7
   ConcentraciónThe filtrate was concentrated under reduced pressure
8. 8
   Otroto give the crude material which
9. 9
   FiltraciónThe whole mixture was filtered through a filter
10. 10
    FiltraciónThe solids filtered off
11. 11
    workup.ADDITIONwere diluted with EtOAc (300 mL)
12. 12
    Filtraciónfiltered again
13. 13
    FiltraciónThis process with the solids filtered off
14. 14
    Lavadowashed with sat'd aq NaHCO3 (300 mL)
15. 15
    Secadodried over MgSO4
16. 16
    Filtraciónfiltered
17. 17
    Lavadowhile rinsing with EtOAc
18. 18
    Concentraciónconcentrated under reduced pressure
19. 19
    Otroto give the crude material that
20. 20
    Otrowas triturated with ether (100 mL)

Procedimiento

A mixture of (E)-ethyl 3-(4-bromo-2-nitrophenyl)-2-(cyanomethyl)acrylate (20.0 g, 59.0 mmol) in AcOH (380 mL) was heated to 80° C. To this mixture iron (19.8 g, 354 mmol) was added portionwise over 1 h keeping the internal temperature below 100° C. After completion of addition of iron, the reaction mixture was heated for additional 2.5 h at 80-85° C. until the starting material disappeared on HPLC. The reaction mixture was cooled to room temperature and filtered through a GF/F filter packed with Celite rinsing with AcOH. The filtrate was concentrated under reduced pressure to give the crude material which was diluted with water (150 mL). The aqueous mixture was treated with sat'd NaHCO3 (200 mL) until it became basic (pH>8). To the suspension was added additional EtOAc (350 mL). The whole mixture was filtered through a filter packed with Celite. The solids filtered off were diluted with EtOAc (300 mL), stirred for 15 min, and filtered again. This process with the solids filtered off was repeated one more time. All of the organic layers were combined and washed with sat'd aq NaHCO3 (300 mL) followed by brine (300 mL), dried over MgSO4, filtered while rinsing with EtOAc, and concentrated under reduced pressure to give the crude material that was triturated with ether (100 mL) to afford 16.5 g (91%) of (1E,4E)-ethyl 2-amino-8-bromo-3H-benzo[b]azepine-4-carboxylate.

Fuente