反应详情

A mixture of tert-butyl{1-[2-(7-bromo-2-oxoquinolin-1(2H)-yl)ethyl]piperidin-4-yl}carbamate (Intermediate 16) (9.85 g, 21.9 mmol) and potassium cyanide (2.14 g, 32.8 mmol) in dry acetonitrile (60 mL) was degassed and flushed with nitrogen three times. Tributyltinchloride (0.059 mmol, 1.13 mL of a 51.6 mM solution in heptane) was added, followed by 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (63 mg, 0.11 mmol) and tris(dibenzylideneacetone)dipalladium (0) (100 mg, 0.11 mmol) and it was degassed and flushed with nitrogen like above. The mixture was stirred for 30 minutes at room temperature and then degassed and flushed with nitrogen again. It was heated at 85° C. for 20 hours. The solvent was removed under reduced pressure and the residue taken up in dichloromethane (500 mL) and washed with water (200 mL). The aqueous phase was back-extracted once with dichloromethane (200 mL) and combined organic phases were dried over sodium sulfate. Solvent was removed under reduced pressure and the residue was crystallized from acetonitrile (60 mL) to give the product as a colorless solid, 6.57 g (76%), mp 202° C.

1. customwas degassed
2. customflushed with nitrogen three times
3. additionTributyltinchloride (0.059 mmol, 1.13 mL of a 51.6 mM solution in heptane) was added
4. customwas degassed
5. customflushed with nitrogen like above
6. customdegassed
7. customflushed with nitrogen again
8. temperatureIt was heated at 85° C. for 20 hours
9. customThe solvent was removed under reduced pressure
10. washwashed with water (200 mL)
11. extractionThe aqueous phase was back-extracted once with dichloromethane (200 mL)
12. dry with materialwere dried over sodium sulfate
13. customSolvent was removed under reduced pressure
14. customthe residue was crystallized from acetonitrile (60 mL)