反应详情

温度

45 °C

Tert-butyl 10-(hydroxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (1.35 g, 4.71 mmol), K2CO3 (3.26 g, 23.6 mmol) and 1-bromobut-2-yne (495 μL, 5.66 mmol) were combined in N,N-dimethylformamide (15 mL) and heated for 48 h at 45° C. under nitrogen. The reaction mixture was diluted with ethyl acetate (150 mL) and filtered. The filtrate was washed with water, 50% saturated sodium bicarbonate solution, and brine. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The desired fractions obtained from silica gel chromatography (5-20% methanol/dichloromethane) were combined and concentrated, then brought up in ethyl acetate, filtered and concentrated in vacuo to provide tert-butyl-8-but-2-ynyl-10-(hydroxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (1.12 g, 3.31 mmol, 70%). ESI-MS m/z calc. 338.2. found 339.3 (M+1)+; Retention time: 0.86 minutes (3 min run).

1. filtrationfiltered
2. washThe filtrate was washed with water, 50% saturated sodium bicarbonate solution, and brine
3. dry with materialThe organic layer was dried over Na2SO4
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe desired fractions obtained from silica gel chromatography (5-20% methanol/dichloromethane)
7. concentrationconcentrated
8. filtrationfiltered
9. concentrationconcentrated in vacuo