[CH3:1][C:2]1[C:7]([O:8][C:9]2[CH:14]=[CH:13][C:12](N)=[CH:11][C:10]=2[F:16])=[CH:6][CH:5]=[C:4]([CH3:17])[N:3]=1.N([O-])=O.[Na+].C(=O)([O-])[O-].[K+].[K+].CCOC(C)=O.[BrH:34]>O.[Cu]Br>[Br:34][C:12]1[CH:13]=[CH:14][C:9]([O:8][C:7]2[C:2]([CH3:1])=[N:3][C:4]([CH3:17])=[CH:5][CH:6]=2)=[C:10]([F:16])[CH:11]=1To a solution of intermediate 10 (7.7 g, 33.2 mmol) in HBr (75 ml, 48% aqueous), cooled to 0° C., a solution of sodium nitrite (4.57 g, 66.3 mmol) in water (75 ml) was dropwise added over 45 minutes. The reaction mixture was warmed to room temperature and further stirred for 15 minutes. The mixture was cooled to 0° C. and copper (I) bromide (4.0 g, 28.4 mmol) was added portionwise. Stirring was continued for 15 minutes at 0° C. and then the mixture was warmed to room temperature and further stirred for 15 minutes. The reaction mixture was then heated at 140° C. for 1.5 hours. The mixture was cooled to room temperature and carefully neutralized with an aqueous saturated solution of potassium carbonate. EtOAc was then added and layers were separated. The organic phase was dried (Na2SO4) and evaporated till dryness. The crude product was purified by column chromatography (silica gel; heptane to heptane/EtOAc up to 10% as eluent). The desired fractions were collected and evaporated in vacuo to yield intermediate 11 (8.75 g, 89%).
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