反应详情

温度

100 °C

4-Hydroxymethyl-4-phenylpiperidine (0.172 g, 0.9 mmol), palladium(II) acetate (0.007 g, 0.03 mmol), cesium carbonate (0.391 g, 1.2 mmol) and Xantphos (0.035 g, 0.06 mmol) were added to a solution of intermediate D9 (0.2 g, 0.6 mmol) in trifluoromethylbenzene (2 ml). The reaction mixture was heated at 100° C. for 24 hours in a sealed tube, after which it was cooled to room temperature. Subsequently, it was diluted with DCM, H2O (5 ml) and extracted with EtOAc (3×5 ml). The mixture was filtered through diatomaceous earth, and the filtrate was evaporated to dryness. The crude product was purified first by column chromatography (silica gel; eluent: DCM/EtOAc from 90/10 to 0/100) and then by reversed phase HPLC. The desired fractions were collected, evaporated in vacuo and finally freeze dried to yield compound E22 (0.041 g, 18%) as a white foam.

1. temperatureafter which it was cooled to room temperature
2. extractionextracted with EtOAc (3×5 ml)
3. filtrationThe mixture was filtered through diatomaceous earth
4. customthe filtrate was evaporated to dryness
5. customThe crude product was purified first by column chromatography (silica gel; eluent: DCM/EtOAc from 90/10 to 0/100)
6. customThe desired fractions were collected
7. customevaporated in vacuo
8. customfinally freeze dried
9. customto yield compound E22 (0.041 g, 18%) as a white foam