反应详情

4-(2-Chlorophenoxy)-piperidine-1-carboxylic acid tert-butyl ester (10.6) This compound was prepared from 4-hydroxypiperidine-1-carboxylic acid tert-butyl ester (9) (3.505 g; 17.4 mmol), 2-chloro-phenol (3.375 g; 26.3 mmol), triphenylphosphine (6.002 g; 22.9 mmol) and DIAD (4.30 mL; 21.8 mmol) in a manner analogous to 10.5. After 8 days, EtOAc (200 mL) was added to the crude reaction mixture and the solution washed with 50% saturated NaHCO3 (50 mL), saturated NaHCO3 (2×25 mL) and saturated NaCl (2×25 mL) then dried (MgSO4), filtered and concentrated to a viscous liquid. Ether (50 mL) and hexanes (50 mL) were added and this was allowed to stand overnight; whereupon the precipitate was removed by filtration and the filtrate partially concentrated. More material precipitated, which was also removed by filtration, and the filtrate was concentrated to an oil. The product was partially purified on basic alumina (160 mL), eluting with 8:1 hexanes:EtOAc, giving a clear, colorless viscous liquid (5.12 g; 94% crude yield). LC (method A) tR=11.50 min; ESIMS 312.1/314.1 (1/0.3) [MH+], 296.9/298.9 (100/34) [MH+−C4H9+CH3CN], 255.9/257.8 (41/12) [MH+−C4H9], 212.0/214.0 (4/1) [MH+−C4H9−CO2]

1. customreaction mixture
2. washthe solution washed with 50% saturated NaHCO3 (50 mL), saturated NaHCO3 (2×25 mL) and saturated NaCl (2×25 mL)
3. dry with materialthen dried (MgSO4)
4. filtrationfiltered
5. concentrationconcentrated to a viscous liquid
6. additionEther (50 mL) and hexanes (50 mL) were added
7. waitto stand overnight
8. customwhereupon the precipitate was removed by filtration
9. concentrationthe filtrate partially concentrated
10. customMore material precipitated
11. customwhich was also removed by filtration
12. concentrationthe filtrate was concentrated to an oil
13. customThe product was partially purified on basic alumina (160 mL)
14. washeluting with 8:1 hexanes
15. customEtOAc, giving a clear, colorless viscous liquid (5.12 g; 94% crude yield)