反应详情

To a solution of 0.58 g (1.48 mmol) 2-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-ethanol (Ex. 1, int. c) in 6 mL N,N-dimethylformamide, 71 mg (1.5 mmol, 55% dispersion in mineral oil) sodium hydride and after 5 min. 0.32 g (1.78 mmol) bromomethylcyclohexane were added. The reaction mixture was warmed to 50° C. and after 4 h another 71 mg sodium hydride and 0.32 g (1.78 mmol) bromomethylcyclohexane were added. A third batch sodium hydride and bromomethylcyclohexane were added after 3 h. After stirring overnight the reaction mixture was poured on water and ethyl acetate, extracted, the aqueous phase extracted twice with ethyl acetate and the aqueous phase extracted twice with ethyl acetate. The combined organic layers were washed twice with water and once with brine, dried over magnesium sulfate and evaporated. The crude product was purified by silica gel column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:ethylacetate (1:0 to 4:1) to yield the title compound as a white solid (39%). MS (Turbo Spray): m/z=487.3 [M+H].

1. additionwere added
2. extractionextracted
3. extractionthe aqueous phase extracted twice with ethyl acetate
4. extractionthe aqueous phase extracted twice with ethyl acetate
5. washThe combined organic layers were washed twice with water and once with brine
6. dry with materialdried over magnesium sulfate
7. customevaporated
8. customThe crude product was purified by silica gel column chromatography
9. washeluting with a gradient of n-heptane:ethylacetate (1:0 to 4:1)