反应详情

A solution of 3-[5-(2-fluoro-phenyl)-1H-benzimidazol-2-yl]-1,8-dioxa-2-aza-spiro[4.5]dec-2-ene (98.8 mg, 0.281 mmol, as prepared in the previous step) in EtOH (5 mL) was treated with HCl (56.2 μL, 0.281 mmol, 5 M in isopropanol) at rt for 2 h. The mixture was concentrated in vacuo and the residue was dissolved in a minimum amount of EtOH (2.5 mL) with sonication and heating. The solution was cooled to rt, and hexanes were added dropwise until the solution became cloudy. The solution was allowed to sit for 2 min then was treated with additional hexanes. The resulting precipitate was filtered, washed with hexanes, and air-dried to afford the title compound (63.7 mg, 58%) as a white solid. 1H-NMR (400 MHz, d4-MeOH) δ: 7.85 (s, 1H), 7.77-7.83 (m, 1H), 7.70-7.77 (m, 1H), 7.46-7.53 (m, 1H), 7.32-7.41 (m, 1H), 7.21-7.27 (m, 1H), 7.13-7.21 (m, 1H), 3.78-3.88 (m, 2H), 3.63-3.73 (m, 2H), 3.32-3.36 (m, 2H), 1.85-1.98 (m, 4H). Mass Spectrum (LCMS, APCI pos.): Calcd. for C20H18FN3O2: 352.1 (M+H). found: 352.3.

1. concentrationThe mixture was concentrated in vacuo
2. dissolutionthe residue was dissolved in a minimum amount of EtOH (2.5 mL) with sonication
3. temperatureheating
4. additionhexanes were added dropwise until the solution
5. additionthen was treated with additional hexanes
6. filtrationThe resulting precipitate was filtered
7. washwashed with hexanes
8. customair-dried