反应详情

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.

1. stirringAfter stirring for additional 6 h
2. concentrationthe resulting mixture was concentrated under reduced pressure
3. customto give the crude material that
4. extractionto extract the crude product out of the sticky suspension
5. customThe solids formed during acidification
6. filtrationwere filtered off
7. filtrationfilter
8. customThe aqueous layer was separated
9. extractionextracted with CH2Cl2 (3×100 mL)
10. dry with materialThe combined organic layers were dried over MgSO4
11. filtrationfiltered
12. concentrationconcentrated under reduced pressures