反应详情

A solution of N-acetyl-4-hydroxypiperidine (30.5 g.) in dimethylformamide (200 ml.) is added dropwise to a stirred suspension of sodium hydride (11.26 g., 50% dispersion in mineral oil) in dimethylformamide (300 ml.) under an atmosphere of nitrogen. The reaction temperature is kept below 30° C. by external cooling and, after the addition is complete, stirring is continued for a further 11/4 hours. A solution of 1-bromo-3-methoxypropane (35.2 g.) in dimethylformamide (100 ml.) is then added dropwise with external cooling, and the resulting clear solution is stirred at room temperature overnight. The reaction mixture is then evaporated in vacuo, the residue partitioned between water and chloroform, the organic extracts dried (Na2SO4) and evaporated to leave a crude residue. The above aqueous phase is saturated with sodium chloride, further extracted with chloroform, and the organic phase is dried (Na2SO4), and evaporated to leave a further residue. This residue is combined with the original residue and heated on a steam bath overnight with hydrochloric acid (243 ml., 2N). The reaction mixture is extracted with chloroform to remove the residual mineral oil, the aqueous phase concentrated, basified with sodium hydroxide (pH 12), then reextracted with chloroform. The organic extracts are washed with brine, dried (Na2SO4) and evaporated to afford the desired product.

1. customis kept below 30° C.
2. temperatureby external cooling
3. additionafter the addition
4. custom4 hours
5. stirringthe resulting clear solution is stirred at room temperature overnight
6. customThe reaction mixture is then evaporated in vacuo
7. customthe residue partitioned between water and chloroform
8. dry with materialthe organic extracts dried (Na2SO4)
9. customevaporated
10. customto leave a crude residue
11. extractionfurther extracted with chloroform
12. dry with materialthe organic phase is dried (Na2SO4)
13. customevaporated
14. customto leave a further residue
15. extractionThe reaction mixture is extracted with chloroform
16. customto remove the residual mineral oil
17. concentrationthe aqueous phase concentrated
18. washThe organic extracts are washed with brine
19. dry with materialdried (Na2SO4)
20. customevaporated