反应详情

温度

55 °C

A 500 mL round bottom flask with a stirbar was charged with 5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (28.0 g, 0.0996 mol, 1.00 eq), (S)-3-amino-Boc-piperidine (21.75 g, 0.109 mol, 1.09 eq), tris(dibenzylideneacetone)dipalladium (4.75 g, 5.18 mmol, 0.052 eq), racemic BINAP (7.44 g, 12.0 mmol, 0.12 eq), and sodium tert-butoxide (28.7 g, 0.299 mol, 3.00 eq). The flask containing the solids was then evacuated and back-filled with nitrogen three times to degas. Pyridine (200 mL) was then added, and the flask was again purged three times with vacuum and nitrogen. The dark greenish mixture was then stirred at 55° C. overnight under a nitrogen atmosphere. In the morning, the reaction was cooled to room temperature, diluted with 250 mL EtOAc, washed three times with 250 mL portions of 10% NaHSO4, and the organic phase was evaporated. The residue was dissolved in toluene and loaded onto a silica column that had been packed with heptane. The column was washed with 5 column volumes of heptane, after which the desired product was eluted with EtOAc/heptane, to provide the title compound as a pale yellow foam (2.4 g, 81%).

1. additionThe flask containing the solids
2. customwas then evacuated
3. additionback-filled with nitrogen three times
4. customto degas
5. additionPyridine (200 mL) was then added
6. customthe flask was again purged three times with vacuum and nitrogen
7. temperatureIn the morning, the reaction was cooled to room temperature
8. additiondiluted with 250 mL EtOAc
9. washwashed three times with 250 mL portions of 10% NaHSO4
10. customthe organic phase was evaporated
11. dissolutionThe residue was dissolved in toluene
12. washThe column was washed with 5 column volumes of heptane
13. washafter which the desired product was eluted with EtOAc/heptane