N(OC(C)(C)C)=O.[F:8][C:9]1[C:18]([F:19])=[CH:17][C:12]2[NH:13][C:14](N)=[N:15][C:11]=2[CH:10]=1.[ClH:20]>CC(C)=O.[Cu](Cl)Cl>[Cl:20][C:14]1[NH:13][C:12]2[CH:17]=[C:18]([F:19])[C:9]([F:8])=[CH:10][C:11]=2[N:15]=1The procedure used was similar to that reported in J. Med. Chem. 40:811–818, 1997. To a mixture of copper(II) chloride (795 mg, 5.91 mmol) in acetone (20 mL) was added tert-butyl nitrite (0.53 mL, 4.43 mmol). The reaction mixture was stirred at rt for 20 minutes, 5,6-difluoro-1H-benzimidazol-2-amine (500 mg, 2.96 mmol) was then added, and the mixture was heated at reflux for 2 h (with additional portions of tert-butyl nitrite added every 0.5 h). The reaction mixture was then cooled to rt, treated with 2 N HCl, and extracted with ethyl acetate. The organic phase was dried over sodium sulfate and concentrated in vacuo to afford 2-chloro-5,6-difluoro-1H-benzimidazole (580 mg, 73%), which was used without further purification in the next step. LC-MS m/z 189.2 (MH+), ret. time 1.96 min; 1H NMR (300 MHz, DMSO-d6) δ 7.62 (t, 2H), 13.5 (br s, 1H).
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