N([O-])=O.[Na+].[Br:5][C:6]1[CH:12]=[CH:11][C:9]([NH2:10])=[CH:8][C:7]=1[CH3:13].CC([O-])=O.[Na+].[CH2:19]([CH:21](C(=O)C)[C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH3:20].[OH-].[K+].BrC1C(C)=C2C(=CC=1)NC(C(OCC)=O)=C2C>O.CCO>[Br:5][C:6]1[CH:12]=[C:11]2[C:9](=[CH:8][C:7]=1[CH3:13])[NH:10][C:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[C:19]2[CH3:20]
A solution of NaNO2 (1.52 g, 22 mmol) in water (4 mL) was added to a vigorously stirred mixture of 4-bromo-3-methylaniline (3.72 g, 20 mmol) at −5° C. After 30 min stirring, the solution was adjusted to pH 5 with NaOAc (1.40 g). A cold solution of ethyl 2-ethyl-3-oxobutanoate (4.0 g, 22 mmol) and KOH (1.36 g, 22 mmol) in EtOH (16 mL) were added followed by crushed ice (30 g). NaOAc was added if necessary to adjust the pH to 5. The mixture was stirred for 5 h at 0° C. then kept at this temperature overnight. The solution was extracted with EtOAc, washed with brine, dried and evaporated to 8 mL. This solution was added to a solution of HCl (25 mL, 7M in EtOH). It was further refluxed for 3 h. Upon cooling in an ice bath, water (200 mL) was added slowly. The precipitate was filtered, washed with water and dried to afford 5.36 g (91%) as a 1:1 mixture of the title compound and its ethyl 5-bromo-3,4-dimethyl-1H-indole-2-carboxylate isomer. 1H NMR (300 MHz, CDCl3), δ, mix 8.66 and 8.54 (2s, br, 1H), 7.83 and 7.23 (2s, 2×0.5H), 7.42 and 7.05 (2d, J=8.7 Hz, 2×0.5H), 4.41 (q, J=7.2 Hz, 2H), 2.81, 2.79, 2.53 and 2.49 (4s, 4×1.5H), 1.42 (t, J=7.2 Hz, 3H).
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