反应详情

To a chilled solution of 1-benzyl-4-tert-butoxycarbonylaminopiperidine (6.8 g, 23.4 mmol) in DMF (200 mL) was added sodium hydride (0.6 g, 60% dispersion in mineral oil). After 30 min, 1,7-dibromoheptane was added (12 mL) and the reaction mixture was stirred for 24 h. Another portion of sodium hydride (0.6 g, 60% dispersion in mineral oil) was added and the reaction mixture was stirred for 18 h. The DMF was removed in vacuo and the residue extracted with dichloromethane and 1 N HCl (3×). The organic phase was washed with saturated brine, dried over sodium sulfate, filtered and concentrated to give 18.5 g of the crude intermediate. This crude product was purified by silica gel column chromatography, eluting with 1% methanol in dichloromethane. The appropriate fractions were combined and concentrated to afford 4.7 g of the title intermediate (85% pure by HPLC, MS and NMR), which was used without further purification.

1. stirringthe reaction mixture was stirred for 18 h
2. customThe DMF was removed in vacuo
3. extractionthe residue extracted with dichloromethane and 1 N HCl (3×)
4. washThe organic phase was washed with saturated brine
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customto give 18.5 g of the crude intermediate
9. customThis crude product was purified by silica gel column chromatography
10. washeluting with 1% methanol in dichloromethane
11. concentrationconcentrated