反应详情

温度

95 °C

A pressure vessel containing a magnetic stirbar was charged with phenylmethyl 3-bromo-4-cyanobenzoate (100 mg, 0.32 mmol), 1,1-dimethylethyl(trans-4-aminocyclohexyl)carbamate (69 mg, 0.32 mmol), cesium carbonate (125 mg, 0.38 mmol), XANTPHOS (19 mg, 0.032 mmol), tris(dibenzylideneacetone)dipalladium(0) (15 mg, 0.016 mmol) and dioxane (1.5 mL). The vessel was then sealed and heated to 95° C. The suspension was stirred for approximately 24 h at that temperature and was then allowed to cool to room temperature. The suspension was poured into water, and the resulting aqueous mixture was extracted twice with ethyl acetate. The organic extracts were combined, dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was then purified by column chromatography (4:1 hexanes:ethyl acetate) to provide impure phenylmethyl 4-cyano-3-{[trans-4-({[(1,1-dimethylethyl)oxy]carbonyl}-amino)cyclohexyl]amino}benzoate (71.8 mg, 0.16 mmol) as a yellow powder. This material was carried into the subsequent step without further purification. 1H NMR (400 MHz, CDCl3): 7.45-7.28 (m, 8H), 5.37 (s, 2H), 4.47 (m, 1H), 3.40 (m, 1H), 2.12 (m, 4H), 1.46 (s, 9H), 1.31 (m, 4H).

1. additionA pressure vessel containing a magnetic stirbar
2. customThe vessel was then sealed
3. temperatureto cool to room temperature
4. extractionthe resulting aqueous mixture was extracted twice with ethyl acetate
5. dry with materialdried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue was then purified by column chromatography (4:1 hexanes:ethyl acetate)