تفاعل #66263

ord-8ab732eb934048eda5128705219d5b1f

المذيبات

ظروف التفاعل

الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    workup.STIRRINGAfter stirring for additional 6 h
  2. 2
    تركيزthe resulting mixture was concentrated under reduced pressure
  3. 3
    أخرىto give the crude material that
  4. 4
    استخلاصto extract the crude product out of the sticky suspension
  5. 5
    أخرىThe solids formed during acidification
  6. 6
    ترشيحwere filtered off
  7. 7
    ترشيحfilter
  8. 8
    أخرىThe aqueous layer was separated
  9. 9
    استخلاصextracted with CH2Cl2 (3×100 mL)
  10. 10
    تجفيفThe combined organic layers were dried over MgSO4
  11. 11
    ترشيحfiltered
  12. 12
    تركيزconcentrated under reduced pressures

الإجراء التجريبي

To a solution of (1E,4E)-ethyl 2-(tert-butoxycarbonylamino)-8-(4-(pyrrolidine-1-carbonyl)phenyl)-3H-benzo[b]azepine-4-carboxylate (12.0 g, 23.8 mmol) in THF-EtOH (60 mL/60 mL) was added 4 N aq. LiOH (23.8 mL, 95.3 mmol) at 0° C. The reaction mixture was warmed to room temperature and stirred for 21 h. Additional 6 mL of 4 N aq LiOH was added twice after 21 h and 24 h. After stirring for additional 6 h, the resulting mixture was concentrated under reduced pressure to give the crude material that was diluted with water (50 mL) and acidified to a pH of ˜3.5 with 1 N aq phosphoric acid (˜450 mL). ˜250 mL of CH2Cl2 was added during acidification to extract the crude product out of the sticky suspension. The solids formed during acidification were filtered off using a glass filter packed with Celite. The aqueous layer was separated and extracted with CH2Cl2 (3×100 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated under reduced pressures to give 10.2 g (90%) of the crude (1E,4E)-2-(tert-butoxycarbonylamino)-8-(4-(pyrrolidine-1-carbonyl)phenyl)-3H-benzo[b]azepine-4-carboxylic acid that was used directly without further purification. MS APCI(+) m/z 476 (M+1) detected.

المصدر

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