反应详情

温度

90 °C

In a round bottom flask, 2-aminoimidazole sulfate (0.264 g, 1.0 mmol) is added to ethyl 3,3-dimethoxypropionate (0.296 g, 2.0 mmol). Piperidine (5 μL) and EtOH (5 mL) are then added and the flask is heated to reflux overnight. At RT, p-toluenesulfonic acid monohydrate (15 mg) is added and the reaction is returned to reflux for 6 h. At RT, freshly powdered K2CO3 (0.415 g, 3.0 mmol) is added and the reaction is heated to reflux overnight. The reaction is then concentrated to dryness and the residue is triturated with CHCl3 (10 mL) and again concentrated to dryness. The residue is treated with POCl3 (2.0 mL, 21.5 mmol) and heated to 90° C. for 1.5 h, and then to 115° C. for 1 h. At RT, the reaction is concentrated to dryness, and then dissolved in CH2Cl2 and washed with NaHCO3 (sat.) followed by brine. The organic solution is dried over Na2SO4, filtered and concentrated to dryness. The residue is purified via silica gel chromatography using EtOAc to afford the title compound. 1H NMR (400 MHz, CDCl3 with 5% CD3OD (v/v)) δ 8.44 (dd, J=6.8, 0.8, 1H), 7.70 (d, J=0.8, 1H), 7.57 (bs, 1H), 6.92 (dd, J=6.8, 0.8, 1H).

1. temperaturethe flask is heated
2. temperatureto reflux overnight
3. temperatureto reflux for 6 h
4. temperaturethe reaction is heated
5. temperatureto reflux overnight
6. concentrationThe reaction is then concentrated to dryness
7. customthe residue is triturated with CHCl3 (10 mL)
8. concentrationagain concentrated to dryness
9. concentrationAt RT, the reaction is concentrated to dryness
10. dissolutiondissolved in CH2Cl2
11. washwashed with NaHCO3 (sat.)
12. dry with materialThe organic solution is dried over Na2SO4
13. filtrationfiltered
14. concentrationconcentrated to dryness
15. customThe residue is purified via silica gel chromatography