C(OC(=O)/[CH:5]=[C:6]1/[C:7]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:8]=2[O:9][CH2:10][C:11]2[C:16]([F:17])=[CH:15][CH:14]=[CH:13][C:12]/1=2)C.[OH-].[Na+].C([O-])(=O)C.[Li+].[Br:31]N1C(=O)CCC1=O.S([O-])([O-])(=O)=S.[Na+].[Na+].C(=O)(O)[O-].[Na+]>CO.C(#N)C.O>[Br:31]/[CH:5]=[C:6]1/[C:7]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:8]=2[O:9][CH2:10][C:11]2[C:16]([F:17])=[CH:15][CH:14]=[CH:13][C:12]/1=2Heat a stirred slurry of (E)-(3,7-difluoro-6H-dibenzo[b,e]oxepin-11-ylidene)-acetic acid ethyl ester (601 mmol, 190 g) in methanol (1.9 L) and 5 N sodium hydroxide (1.20 mol, 240 mL) to 50° C. for 2 h. Remove the methanol in vacuo and reslurry the resulting black sludge in water (3 L). Add 5 N hydrochloride acid (250 mL) over 45 min, stir for 2.5 h, filter, and rinse the residue with water (4×200 mL). Dry the gray solid in vacuo at 60° C. overnight, and 80° C. for 6 h. Dissolve the solid (still wet, contains approximately 95 g of water) and lithium acetate (60.1 mmol, 4 g, 0.1 eq) in acetonitrile (1.7 L) and stir for 15 min. Add N-bromosuccinimide (661 mmol, 118 g) in one portion and stir for 2.5 h. Add 0.25 M sodium thiosulfate (400 mL), followed by saturated aqueous sodium bicarbonate (400 mL), and water (900 mL). Stir the mixture for one hour at room temperature and then stir for 2 h on an ice bath. Filter the mixture and rinse with cold acetonitrile (300 mL). Dry overnight in vacuo at 50° C. to obtain the title compound as a light beige solid (173.3 g, 89%). 1H NMR (DMSO-d6) δ 5.25 (s, 2H), 6.67 (dd, 1H), 6.81 (dt, 1H), 7.20 (s, 1H), 7.22 (d, 1H), 7.28 (t, 1H), 7.36 (dd, 1H), 7.48 (m, 1H).
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