反应详情

温度

50 °C

2,3-Difluoro-5-iodobenzoic acid (3.0 g, 10.6 mmol) obtained in Step 1 was dissolved in toluene, and thionyl chloride (3.0 ml, 41.1 mmol) and DMF (catalytic amount) were added. The mixture was heated under reflux for 3 hrs. The reaction solution was concentrated under reduced pressure and THF (15 ml) was added to dissolve the residue. The resulting solution was added dropwise to a solution of ethyl 3-dimethylaminoacrylate (1.66 g, 11.6 mmol) and triethylamine (1.77 ml, 12.7 mmol) in THF (10 ml) and the mixture was stirred with heating at 50° C. for 2.5 hrs. After allowing the mixture to cool, the reaction mixture was filtered and washed with THF (10 ml). Aminoethanol (0.77 ml, 12.7 mmol) was added to the filtrate and the mixture was stirred with heating at 40° C. for 1 hr. After allowing the mixture to cool, water was added to the reaction solution and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the obtained residue was purified by silica gel chromatography (ethyl acetate:hexane=2:1) to give an object product (3.8 g, yield 85%). of a mixture of E form and Z form as a yellow solid.

1. temperatureThe mixture was heated
2. temperatureunder reflux for 3 hrs
3. concentrationThe reaction solution was concentrated under reduced pressure and THF (15 ml)
4. additionwas added
5. dissolutionto dissolve the residue
6. temperatureto cool
7. filtrationthe reaction mixture was filtered
8. washwashed with THF (10 ml)
9. stirringthe mixture was stirred
10. temperaturewith heating at 40° C. for 1 hr
11. temperatureto cool
12. extractionthe mixture was extracted with ethyl acetate
13. washThe organic layer was washed with water and saturated brine
14. dry with materialdried over sodium sulfate
15. filtrationAfter filtration
16. concentrationthe filtrate was concentrated under reduced pressure
17. customthe obtained residue was purified by silica gel chromatography (ethyl acetate:hexane=2:1)