反应详情

4-(4-Amino-2-fluorophenoxy)pyridine-2-carboxylic acid methyl ester (11.5 g) was dissolved in acetone (340 ml) and water (170 ml). Next, sodium hydrogencarbonate (17.3 g) was added to the reaction mixture, benzyl chloroformate (9.79 ml) was added while cooling in an ice water bath, and the mixture was stirred for 15 minutes. The reaction mixture was allowed to warm to room temperature and then the mixture was stirred for 2 hours. Benzyl chloroformate (2.45 ml) was further added to the reaction mixture while cooling in an ice water bath, and the mixture was stirred for 18 hours. After concentrating the reaction mixture under reduced pressure, ethyl acetate (500 ml) and brine (200 ml) were added to the resultant residue for partition. The separated organic layer was washed with water (100 ml) and brine (200 ml) and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and then ethyl acetate (50 ml) and hexane (30 ml) were added to the resultant solid for suspension. After filtering the solid, it was subjected to aeration drying to provide the title compound (9.6 g, 70.6%) as a pale yellow solid.

1. additionwas added
2. temperaturewhile cooling in an ice water bath
3. stirringthe mixture was stirred for 2 hours
4. temperaturewhile cooling in an ice water bath
5. stirringthe mixture was stirred for 18 hours
6. concentrationAfter concentrating the reaction mixture under reduced pressure, ethyl acetate (500 ml) and brine (200 ml)
7. additionwere added to the resultant residue
8. customfor partition
9. washThe separated organic layer was washed with water (100 ml) and brine (200 ml)
10. dry with materialdried over anhydrous sodium sulfate
11. distillationThe solvent was distilled off under reduced pressure
12. additionethyl acetate (50 ml) and hexane (30 ml) were added to the resultant solid for suspension
13. filtrationAfter filtering the solid, it
14. customdrying