反应详情

To a solution of 4-amino-piperidine-1-carboxylic acid tert-butyl ester (4.0 g, 20.0 mmol, 1.3 equiv; commercially available) in dry DMF (100 mL) under Ar was added sodium hydride (1.01 g, 23.1 mmol, 1.5 equiv; 55% free-flowing powder moistened with oil) and the reaction mixture stirred at rt. After 2 h 2-chloro-5-(4-methoxy-phenyl)-pyrimidine (3.39 g, 15.4 mmol, 1.0 equiv; commercially available from Peakdale Molecular, UK) was added and the mixture stirred at rt for 48 h. The solvent was removed under reduced pressure and the crude reaction product extracted from a solution of 1 M NaOH (100 mL) with ethyl acetate (3×100 mL). The combined organic phases were dried over MgSO4, concentrated by evaporation under reduced pressure and the crude material purified by silica column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane/ethyl acetate to provide 0.55 g (9%) of the title compound. MS (ISP): 385.4 [M+H]+.

1. additioncommercially available from Peakdale Molecular, UK) was added
2. stirringthe mixture stirred at rt for 48 h
3. customThe solvent was removed under reduced pressure
4. customthe crude reaction product
5. extractionextracted from a solution of 1 M NaOH (100 mL) with ethyl acetate (3×100 mL)
6. dry with materialThe combined organic phases were dried over MgSO4
7. concentrationconcentrated by evaporation under reduced pressure
8. customthe crude material purified by silica column chromatography
9. washeluting with a gradient of heptane/ethyl acetate