反应详情

Hexamethyldisilazane (17.45 mL, 83 mmol) was added dropwise to acetic acid (38.1 mL, 666 mmol) (caution exothermic, maintain below 70° C.) stirred under an atmosphere of nitrogen. The resulting mixture was added to a solution of 1-[3-(methyloxy)phenyl]ethanone (9.14 mL, 66.6 mmol) and ethyl cyanoacetate (11.75 mL, 110 mmol) in acetic acid (16 mL), which was then stirred at 70° C. for 18 h. The mixture was then allowed to cool to RT and DCM (350 mL) and water (125 mL) were added. The organic layer was then separated and washed with additional water (125 mL) and dried with anhydrous MgSO4, filtered and evaporated to dryness. The residue was purified on silica, eluting with a gradient of 0-30% ethyl acetate in isohexane and further purified on silica, eluting with a gradient of 0-25% ethyl acetate in isohexane, to afford the title compound (14.1 g). LCMS (A) m/z: 246 [M+1]+, Rt 1.28 min (basic).

1. stirringwas then stirred at 70° C. for 18 h
2. customThe organic layer was then separated
3. washwashed with additional water (125 mL)
4. dry with materialdried with anhydrous MgSO4
5. filtrationfiltered
6. customevaporated to dryness
7. customThe residue was purified on silica
8. washeluting with a gradient of 0-30% ethyl acetate in isohexane
9. customfurther purified on silica
10. washeluting with a gradient of 0-25% ethyl acetate in isohexane