[Br:1][C:2]1[CH:3]=[CH:4][C:5]2=[C:6]([CH:25]=1)[N:7]=[C:8]([NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:9][C:10]([C:12]([O:14]CC)=[O:13])=[CH:11]2.[OH-].[Na+].Cl>C1COCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2=[C:6]([CH:25]=1)[N:7]=[C:8]([NH:17][C:18]([O:20][C:21]([CH3:23])([CH3:22])[CH3:24])=[O:19])[CH2:9][C:10]([C:12]([OH:14])=[O:13])=[CH:11]2To a solution of (1E,4E)-ethyl 8-bromo-2-(tert-butoxycarbonylamino)-3H-benzo[b]azepine-4-carboxylate (15.0 g, 36.7 mmol) in THF (195 mL) at −15° C. was slowly added 1N aq NaOH (55.0 ml, 55.0 mmol) over 10 min. The reaction mixture was warmed to room temperature and stirred for 18 h. The reaction mixture was poured into ice-cold water (500 mL). The pH of the mixture was carefully adjusted to 5-6 with 0.5 N aq HCl (˜260 mL). The resulting mixture was extracted with EtOAc. The aqueous layer was extracted with EtOAc (1×). The combined organic layers were washed with brine, dried over MgSO4, filtered while rinsing with EtOAc, and concentrated under reduced pressure to give the crude material that was triturated with MeCN (20 mL). The solids were filtered off and dried under reduced pressure to afford 7.56 g (54%) of the desired product. The filtrate was concentrated under reduced pressure again to give the second crude material that was triturated with MeCN again to afford additional 1.33 g (9.5%) of the product. Total 8.89 g (64%) of (1E,4E)-8-bromo-2-(tert-butoxycarbonylamino)-3H-benzo[b]azepine-4-carboxylic acid was obtained. MS APCI(+) m/z 381, 383 (M+1, Br pattern) detected.
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