반응 #10059

반응 방정식

benzaldehyde

4-amino-2-(2,6-dioxo(3-piperidyl))isoindoline-1,3-dione

benzaldehyde

sodium borohydride

sodium borohydride

→

2-(2,6-dioxo(3-piperidyl))-4-[benzylamino]isoindoline-1,3-dione

수율 16.0%

용매

ethyl acetate

sodium hydrogen carbonate

acetic acid

반응 조건

후처리

1. 1
   온도was heated
2. 2
   온도to reflux for 3 h
3. 3
   온도The mixture was cooled to room temperature
4. 4
   workup.WAITkept at room temperature for 18 h
5. 5
   온도The mixture was then heated
6. 6
   온도to reflux for 2 h
7. 7
   온도during reflux
8. 8
   온도After 30 min of reflux the reaction
9. 9
   온도to cool to room temperature
10. 10
    workup.STIRRINGthe mixture stirred at room temperature for 3 days
11. 11
    기타The solvent was removed in vacuo
12. 12
    기타to yield an oil
13. 13
    기타The organic layer was separated
14. 14
    세척was washed with aqueous sodium hydrogen carbonate (sat, 2×100 ml), brine (100 ml)
15. 15
    건조dried over MgSO4
16. 16
    기타The solvent was removed in vacuo
17. 17
    기타to give a solid
18. 18
    기타The solid was purified by column chromatography (Silca Gel, 50% EtOAc:CH2Cl2)
19. 19
    기타to give a yellow solid
20. 20
    기타The solid was further purified by column chromatography (KP-C18-HS, 35:65 CH3CN:0.1% CF3COOH in water)

실험 절차

A mixture of 4-amino-2-(2,6-dioxo(3-piperidyl))isoindoline-1,3-dione (1.0 g, 3.7 mmol) and benzaldehyde (0.4 ml, 3.9 mmol) in acetic acid (20 ml) was stirred at room temperature for 17 h, then was heated to reflux for 3 h. The mixture was cooled to room temperature. To the stirred mixture was added sodium borohydride (140 mg, 3.7 mmol) and kept at room temperature for 18 h. The mixture was then heated to reflux for 2 h. To the mixture was added additional benzaldehyde (0.4 ml, 3.9 mmol) during reflux. After 30 min of reflux the reaction was allowed to cool to room temperature. To the mixture was added sodium borohydride (180 mg, 4.8 mmol) and the mixture stirred at room temperature for 3 days. The solvent was removed in vacuo to yield an oil. The oil was diluted with ethyl acetate (90 ml) and aqueous sodium hydrogen carbonate (sat, 100 ml). The organic layer was separated and was washed with aqueous sodium hydrogen carbonate (sat, 2×100 ml), brine (100 ml) and dried over MgSO4. The solvent was removed in vacuo to give a solid. The solid was purified by column chromatography (Silca Gel, 50% EtOAc:CH2Cl2) to give a yellow solid. The solid was further purified by column chromatography (KP-C18-HS, 35:65 CH3CN:0.1% CF3COOH in water) to give 2-(2,6-dioxo(3-piperidyl))-4-[benzylamino]isoindoline-1,3-dione as a yellow solid (210 mg, 16% yield): mp, 209–211° C.; 1H NMR (DMSO-d6) δ 2.02–2.08 (m, 1H, CHH), 2.46–2.63 (m, 2H, CH2), 2.82–2.97 (m, 1H, CHH), 4.56 (d, J=6.2 Hz, 2H, CH2), 5.07 (dd, J=5.3, 12.4 Hz, 1H, NCH), 6.96 (d, J=8.6 Hz, 1H, Ar), 7.02 (d, J=7.0 Hz, 1H, Ar), 7.19–7.40 (m, 6H, Ar, NH), 7.51 (dd, J=7.5, 8.4 Hz, 1H, Ar), 11.11 (s, 1H, NH); 13C NMR (DMSO-d6) δ 22.15, 30.99, 45.44, 48.59, 109.58, 110.74, 117.63, 126.95, 126.99, 132.21, 136.09, 138.95, 146.09, 167.27, 168.78, 170.07, 172.79; Anal Calcd for C20H17N3O4: C, 66.11; H, 4.72; N, 11.56. Found: C, 65.96; H, 4.60; N, 11.49.

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