反应详情

To a 1-liter three-necked round-bottom flask equipped with overhead stirrer, temperature control and addition funnel was added methyl 4-amino-5-chloro-2-methoxybenzoate (44.2 g, 200 mmol), dichloromethane (500 mL) and diisopropylethylamine (104.5 mL, 600 mmol). The resulting mixture was stirred at room temperature until the ingredients dissolved and then the mixture was cooled to 0° C. Acryloyl chloride (16.25 mL, 200 mmol) was then added dropwise while maintaining the internal reaction mixture temperature below 10° C. The total time for addition was about 30 min. The reaction mixture was then slowly warmed from 0° C. to room temperature over a period of about 2 hours. Aqueous saturated sodium bicarbonate solution (200 mL) and dichloromethane (200 mL) were then added and this mixture was stirred for 15 min. and then the layers were separated. The dichloromethane layer was washed with 1 M hydrochloric acid (200 mL) and then concentrated under reduced pressure to about one-third its original volume resulting in a thick slurry. The slurry was filtered and the filter cake was washed with dichloromethane (100 mL) and dried to provide the title compound as an off-white solid (36 g, 67% yield, >98% purity by HPLC).

1. customTo a 1-liter three-necked round-bottom flask equipped with overhead stirrer
2. additiontemperature control and addition funnel
3. dissolutiondissolved
4. temperaturethe mixture was cooled to 0° C
5. temperaturewhile maintaining the internal reaction mixture temperature below 10° C
6. additionThe total time for addition
7. temperatureThe reaction mixture was then slowly warmed from 0° C. to room temperature over a period of about 2 hours
8. stirringthis mixture was stirred for 15 min.
9. customthe layers were separated
10. washThe dichloromethane layer was washed with 1 M hydrochloric acid (200 mL)
11. concentrationconcentrated under reduced pressure to about one-third its original volume
12. customresulting in a thick slurry
13. filtrationThe slurry was filtered
14. washthe filter cake was washed with dichloromethane (100 mL)
15. customdried