反应详情

温度

-78 °C

To a solution of 3-bromo-2-ethyl-4,5,6,7-tetrahydropyrazolo[1,5-α]pyridine (4.01 g, 17.6 mmol, from Step 3) in THF (20 mL) was added t-BuLi (1.7 M in pentane, 22.8 mL, 38.7 mmol) dropwise at −78° C. After stirring at −78° C. for 30 min., was added tert-butyl 4-oxo-1-piperidinecarboxylate (3.51 g, 17.6 mmol) in THF (10 mL) dropwise at −78° C. The mixture was stirred at −78° C. for 10 min. and at rt for 4 h. After the reaction was quenched with aqueous NH4Cl, the mixture was partitioned between EtOAc and water. Aqueous layer was extracted with EtOAc (3×). Combined organic phase was washed with brine and dried over anhydrous MgSO4. Concentration was followed by purification by flash chromatography (hexanes: EtOAc=1:1, then 100% EtOAc) to give the title compound as a foamy solid. 1H NMR (500 Mz, CDCl3): δ 1.26 (t, 3H, J=7.4 Hz), 1.49 (s, 9H), 1.75-1.90 (m, 4H), 1.90-2.10 (m, 4H), 2.76 (q, 2H, J=7.6 Hz), 2.89 (t, 2H, J=6.4 Hz), 3.10-3.20 (br, 2H), 3.85-4.05 (br, 2H), 4.09 (t, 2H, J=6.2 Hz). ESI-MS 276 (M-t-Bu-H2O+H); HPLC C: 2.05 min.

1. stirringThe mixture was stirred at −78° C. for 10 min. and at rt for 4 h
2. customAfter the reaction was quenched with aqueous NH4Cl
3. customthe mixture was partitioned between EtOAc and water
4. extractionAqueous layer was extracted with EtOAc (3×)
5. washCombined organic phase was washed with brine
6. dry with materialdried over anhydrous MgSO4
7. concentrationConcentration
8. customwas followed by purification by flash chromatography (hexanes