反应详情

温度

100 °C

A mixture of 2-(4-fluorophenyl)imidazo[1,2-a]pyrazine-8-carboxylic acid (Preparation #C.1, 18.9 g, 66.1 mmol) and 1M of hydrogen chloride in water (500 mL) was heated to about 100° C. for about 2 h. The reaction mixture was cooled to ambient temperature and solid Na2CO3 (50.0 g) was added cautiously portion-wise to raise the pH to about 8-9. The resulting brown solid was collected washing with water (4×80 mL). The product in the filtrate was extracted with EtOAc (3×200 mL). In addition the solid was dissolved in EtOAc (1 L) and filtered from insoluble material. The combined organic extracts were washed with water (3×200 mL) and brine (150 mL), then dried over Na2SO4, filtered and concentrated under reduced pressure to yield a brown solid. The solid was stirred with Et2O (8×150 mL); the insoluble solid was filtered each time until no product remained in the insoluble material. The Et2O was evaporated to yield a brown solid, which was dissolved in EtOAc (25 mL) and purified by silica chromatography using the EtOAc as eluent to yield an orange/brown solid (5.12 g, 34.8%): LC/MS (Table 1, Method g) Rt=2.10 min; MS m/z: 214.1 (M+H)+.

1. temperatureThe reaction mixture was cooled to ambient temperature
2. temperatureto raise the pH to about 8-9
3. customThe resulting brown solid was collected
4. washwashing with water (4×80 mL)
5. extractionThe product in the filtrate was extracted with EtOAc (3×200 mL)
6. additionIn addition the solid
7. dissolutionwas dissolved in EtOAc (1 L)
8. filtrationfiltered from insoluble material
9. washThe combined organic extracts were washed with water (3×200 mL) and brine (150 mL)
10. dry with materialdried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated under reduced pressure
13. customto yield a brown solid
14. filtrationthe insoluble solid was filtered each time until no product
15. customThe Et2O was evaporated
16. customto yield a brown solid, which
17. custompurified by silica chromatography