反应详情

温度

60 °C

A mixture of tert-butyl 4,9-diazaspiro[5.5]undecane-9-carboxylate hydrochloride (170.00 g, 584.53 mmoles), cesium carbonate (476.13 g, 1.46 moles), and 4-bromobutyne (93.28 g, 701.43 mmoles) in acetonitrile (1.70 L) is heated to 60° C. and stirred at this temperature overnight. Further 4-bromobutyne (46.64 g, 350.72 mmoles) is added and the mixture is stirred at 60° C. overnight. The mixture is cooled and filtered. The filtrate is concentrated under reduced pressure and the residue dissolved in ethyl acetate (500 mL), washed with water (1 L), and saturated aqueous sodium chloride (1 L), then dried over MgSO4, and filtered. The filtrate is concentrated under reduced pressure and the residue is purified by silica column chromatography eluting with 20 to 70% ethyl acetate in dichloromethane to provide the title compound (129 g, 72% yield). Mass spectrum (m/z): 307.25 (M+1).

1. stirringthe mixture is stirred at 60° C. overnight
2. temperatureThe mixture is cooled
3. filtrationfiltered
4. concentrationThe filtrate is concentrated under reduced pressure
5. dissolutionthe residue dissolved in ethyl acetate (500 mL)
6. washwashed with water (1 L), and saturated aqueous sodium chloride (1 L)
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. concentrationThe filtrate is concentrated under reduced pressure
10. customthe residue is purified by silica column chromatography
11. washeluting with 20 to 70% ethyl acetate in dichloromethane