Ethyl Acetate → ethyl 2-amino-8-bromo-3H-benzo[b]azepine-4-carboxylate

HRID 593440

반응식

HRID 593440 반응식
[Br:1][C:2]1[CH:7]=[CH:6][C:5](/[CH:8]=[C:9](\[CH2:15][C:16]#[N:17])/[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[C:4]([N+:18]([O-])=O)[CH:3]=1.C([O-])(O)=O.[Na+].CCOC(C)=O>CC(O)=O.O.[Fe]>[NH2:17][C:16]1[CH2:15][C:9]([C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:8][C:5]2[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][C:4]=2[N:18]=1

참가 물질

7

반응물 3

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 58228520(E)-ethyl 3-(4-bromo-2-nitrophenyl)-2-(cyanomethyl)acrylate

생성물 1

HCID 58228535ethyl 2-amino-8-bromo-3H-benzo[b]azepine-4-carboxylate수율 91%

시약·촉매·용매 3

HCID 23925Iron촉매2회HCID 176Acetic Acid용매HCID 962Water용매

반응 조건

온도
80 °C

실험 절차

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.

후처리

  1. customthe internal temperature below 100° C
  2. temperaturethe reaction mixture was heated for additional 2.5 h at 80-85° C. until the starting material
  3. temperatureThe reaction mixture was cooled to room temperature
  4. filtrationfiltered through a GF/F
  5. filtrationfilter
  6. washrinsing with AcOH
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customto give the crude material which
  9. filtrationThe whole mixture was filtered through a filter
  10. filtrationThe solids filtered off
  11. additionwere diluted with EtOAc (300 mL)
  12. filtrationfiltered again
  13. filtrationThis process with the solids filtered off
  14. washwashed with sat'd aq NaHCO3 (300 mL)
  15. dry with materialdried over MgSO4
  16. filtrationfiltered
  17. washwhile rinsing with EtOAc
  18. concentrationconcentrated under reduced pressure
  19. customto give the crude material that
  20. customwas triturated with ether (100 mL)

출처 및 근거

ORD 기록
ord-e8e73b951a1448d283d17c41fc6b3734
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09242964B2

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