反应详情

温度

80 °C

To a mixture of 4-acetyl-6-chloro-3-ethoxy-2-iodobenzonitrile (50 mg, 0.1 mmol, Example 318, Step 1), 3-methoxyazetidine hydrochloride (21 mg, 0.17 mmol Chem-Impex catalog#20140) and cesium carbonate (70.0 mg, 0.21 mmol) in 1,4-dioxane (4 mL) was added (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (40 mg, 0.07 mmol) and tris(dibenzylideneacetone)dipalladium (0) (60 mg, 0.07 mmol). The reaction mixture was degassed with N2. The reaction was heated at 80° C. for 2 hrs and was monitored by LC/MS. The reaction was allowed to cool to room temperature, was diluted with water and extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated to give the crude product. The product was purified by FCC on silica gel eluting (hexanes: EtOAc 0-70%) gradient to give to 4-acetyl-6-chloro-3-ethoxy-2-(3-methoxyazetidin-1-yl)benzonitrile as clear oil (0.030 g, 70%). LCMS calculated for C15H18ClN2O3(M+H)+: m/z=309.1; found: 309.1.

1. customThe reaction mixture was degassed with N2
2. temperatureto cool to room temperature
3. additionwas diluted with water
4. extractionextracted with EtOAc
5. washThe combined organic layers were washed with brine
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated
9. customto give the crude product
10. customThe product was purified by FCC on silica gel eluting (hexanes: EtOAc 0-70%) gradient