تفاعل #66280

ord-a83da1c9318343b2a3473e53415fa069

المذيبات

ظروف التفاعل

درجة الحرارة
65°CELSIUS
الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    أخرىwas bubbled with N2 for 10 min
  2. 2
    أخرىThe resulting mixture was bubbled with N2 for 10 min
  3. 3
    درجة الحرارةThe reaction mixture was cooled to room temperature
  4. 4
    تركيزconcentrated under reduced pressure
  5. 5
    أخرىto give the crude material that
  6. 6
    ترشيحThe mixture was filtered through GF/F
  7. 7
    ترشيحfilter
  8. 8
    أخرىThe aqueous layer was separated
  9. 9
    استخلاصextracted with EtOAc (10 mL)
  10. 10
    غسيلThe combined organic layers were washed with brine (10 mL)
  11. 11
    تجفيفdried over MgSO4
  12. 12
    ترشيحfiltered
  13. 13
    تركيزconcentrated under reduced pressure
  14. 14
    أخرىto give the crude product that
  15. 15
    أخرىwas purified by silica gel flash column chromatography (CH2Cl2 to 2% MeOH in CH2Cl2)

الإجراء التجريبي

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.

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US08524702B2uspto-grants-2013_09