반응 #66280

ord-a83da1c9318343b2a3473e53415fa069

반응 조건

온도
65°CELSIUS
상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    기타was bubbled with N2 for 10 min
  2. 2
    기타The resulting mixture was bubbled with N2 for 10 min
  3. 3
    온도The reaction mixture was cooled to room temperature
  4. 4
    농축concentrated under reduced pressure
  5. 5
    기타to give the crude material that
  6. 6
    여과The mixture was filtered through GF/F
  7. 7
    여과filter
  8. 8
    기타The aqueous layer was separated
  9. 9
    추출extracted with EtOAc (10 mL)
  10. 10
    세척The combined organic layers were washed with brine (10 mL)
  11. 11
    건조dried over MgSO4
  12. 12
    여과filtered
  13. 13
    농축concentrated under reduced pressure
  14. 14
    기타to give the crude product that
  15. 15
    기타was purified by silica gel flash column chromatography (CH2Cl2 to 2% MeOH in CH2Cl2)

실험 절차

To Na2CO3 (129 mg, 1.214 mmol) in a 50 mL round-bottom flask was added water (3.7 mL) was bubbled with N2 for 10 min. To this mixture was added tert-butyl (1E,4E)-8-bromo-4-(dipropylcarbamoyl)-3H-benzo[b]azepin-2-ylcarbamate (200 mg, 0.40 mmol) in EtOH (4.9 mL) at room temperature. The resulting mixture was bubbled with N2 for 10 min. Pd(OAc)2 (9.3 mg, 0.040 mmol) and 4,4′-(phenylphosphinidene)bisbenzenesulfonic acid dipotassium hydrate (45 mg, 0.081 mmol) were added. The resulting mixture was warmed to 65° C. with N2 bubbling. To this mixture was added a solution of 4-(dimethylcarbamoyl)phenylboronic acid (97 mg, 0.49 mmol) in EtOH (0.6 mL). The resulting mixture was stirred at 65° C. for 1 h. The reaction mixture was cooled to room temperature and concentrated under reduced pressure to give the crude material that was diluted with water (5 mL) and EtOAc (10 mL). The mixture was filtered through GF/F filter. The aqueous layer was separated and extracted with EtOAc (10 mL). The combined organic layers were washed with brine (10 mL), dried over MgSO4, filtered, and concentrated under reduced pressure to give the crude product that was purified by silica gel flash column chromatography (CH2Cl2 to 2% MeOH in CH2Cl2) to afford 178 mg (83%) of tert-butyl (1E,4E)-8-(4-(dimethylcarbamoyl)phenyl)-4-(dipropylcarbamoyl)-3H-benzo[b]azepin-2-ylcarbamate. MS APCI(+) m/z 533 (M+1) detected.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US08524702B2uspto-grants-2013_09