[F:1][C:2]1[CH:3]=[C:4]([C:9]2[N:13]=[CH:12][O:11][N:10]=2)[CH:5]=[CH:6][C:7]=1[CH3:8].[Br:14]N1C(=O)CCC1=O.C(N(C(C)C)CC)(C)C.P([O-])(OCC)OCC>C(#N)C.N(C(C)(C)C#N)=NC(C)(C)C#N.O>[Br:14][CH2:8][C:7]1[CH:6]=[CH:5][C:4]([C:9]2[N:13]=[CH:12][O:11][N:10]=2)=[CH:3][C:2]=1[F:1]
3-(3-Fluoro-4-methylphenyl)-1,2,4-oxadiazole (101.8 g, 0.57 mol) and N-bromosuccinimide (206 g, 1.16 mol) were dissolved in acetonitrile (˜1 L) and azobisisobutyronitrile (4.2 g, 26 mmol) was added at room temperature. The mixture was heated to 70° C. for 2 hours at which point HPLC showed complete conversion of the starting material to a mixture of the monobromide and dibromide. The mixture was cooled to 0° C. and diisopropyl ethyl amine (73 mL, 54.2 g, 0.42 mol) was added while maintaining the reaction temperature below 5 C. Diethyl phosphite (54.7 mL, 58.6 g, 0.42 mol) was added slowly and the reaction mixture was warmed to room temperature. After 2 hours HPLC showed complete conversion of the dibromide to the monobromide. Water (1.2 L) was added and the resulting precipitate was filtered. Washing with water (2×200 mL) and drying provided 3-(4-(bromomethyl)-3-fluorophenyl)-1,2,4-oxadiazole (135 g, 92% yield).
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