تفاعل #10059

معادلة التفاعل

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

المردود 16.0%

المذيبات

ethyl acetate

sodium hydrogen carbonate

acetic acid

ظروف التفاعل

المعالجة

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

الإجراء التجريبي

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.

المصدر